S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

Rectal Adenocarcinoma Clinical Trial

Official title:

S1613, A Randomized Phase II Study of Trastuzumab and Pertuzumab (TP) Compared to Cetuximab and Irinotecan (CETIRI) in Advanced/Metastatic Colorectal Cancer (mCRC) With HER-2 Amplification

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03365882
• Other study ID #: S1613
• Secondary ID: NCI-2016-01422S1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 27, 2017
• Est. completion date: November 20, 2024

Study information

• Verified date: January 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well trastuzumab and pertuzumab work compared to cetuximab and irinotecan hydrochloride in treating patients with HER2/neu amplified colorectal cancer that has spread from where it started to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as trastuzumab and pertuzumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cetuximab and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trastuzumab and pertuzumab may work better compared to cetuximab and irinotecan hydrochloride in treating patients with colorectal cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of trastuzumab and pertuzumab (TP) (Arm 1) in HER-2 amplified metastatic colorectal cancer (mCRC) by comparing progression-free survival (PFS) on TP compared to control arm (Arm 2) of cetuximab and irinotecan hydrochloride (irinotecan) (CETIRI).

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (ORR), including confirmed complete and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, in treatment Arms 1 and 2.

II. To evaluate the overall survival (OS) in treatment Arms 1 and 2. III. To evaluate the safety and toxicity of TP compared to CETIRI.

TERTIARY OBJECTIVES:

I. To estimate the rates of PFS, OS, and ORR in patients who crossover to TP (Arm 3) after disease progression on CETIRI.

II. To bank images for future retrospective analysis. III. To evaluate if HER-2/centromeric probe (CEP17) signal ratio and HER-2 gene copy number (GCN) are predictive of clinical efficacy for patients receiving TP versus CETIRI.

IV. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.

OUTLINE: Patients with HER2 gene amplification are randomized to 1 of 2 arms.

ARM I: Patients receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may optionally crossover to Arm I.

After completion of study treatment, patients are followed up for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: November 20, 2024
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• STEP 1 INITIAL REGISTRATION: HER2 TESTING

• Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is metastatic or locally advanced and unresectable

• Mutation results:

• All patients must have molecular testing performed in a Clinical Laboratory Improvement Act (CLIA) certified lab which includes which includes KRAS and NRAS gene and exon 15 of BRAF gene (BRAF V600E mutation); patients with any known activating mutation in exon 2 [codons 12 and 13], exon 3 [codons 59 and 61] and exon 4 [codons 117 and 146]) of KRAS/NRAS genes and in exon 15 (BRAFV600E mutation) of BRAF gene are not eligible

• Patients must not have been treated with any of the following prior to step 1 initial registration:

• Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR

• HER-2 targeting for treatment of colorectal cancer; patients who have received prior trastuzumab or pertuzumab for other indications such as prior history of adjuvant or neoadjuvant breast cancer treatment prior to the development of advanced colorectal cancer are eligible

• Patients must not have had history of severe toxicity and intolerance to or hypersensitivity to irinotecan or any other study drug; patients must not have had a severe infusion-related reaction during any prior therapy with pertuzumab or trastuzumab

• Patients must have tumor slides available for submission for HER-2 testing; HER-2 testing must be completed by the central lab prior to step 2 randomization

• Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines; for step 1 initial registration, the appropriate consent form is the step 1 consent form

• As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• STEP 2 RANDOMIZATION

• Patients must have HER-2 amplification as determined by central testing (3+ or 2+ by immunohistochemistry and HER-2 gene amplification by in situ hybridization with a ratio of HER-2 gene signals to centromere 17 signals >= 2.0)

• Patients must have measurable disease that is metastatic or locally advanced and unresectable; imaging used to assess all disease per RECIST 1.1 must have been completed within 28 days prior to step 2 randomization; all disease must be assessed and documented on the Baseline Tumor Assessment Form

• Patients must have had at least one prior regimen of systemic chemotherapy for metastatic or locally advanced, unresectable disease; patients must have progressed following the most recent therapy; prior treatment with irinotecan is allowed; for patients that received adjuvant chemotherapy: prior treatment for metastatic disease is not required for patient who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy; if the patient received one line of adjuvant treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of chemotherapy used to treat the metastatic or locally advanced, unresectable disease; patients who have received >= 3 lines of systemic chemotherapy for metastatic or locally advanced, unresectable disease are not eligible

• Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to step 2 randomization and all toxicity must be resolved to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to step 2 randomization

• Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to step 2 randomization; eligible patients must be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to step 2 randomization

• Patients must have a Zubrod performance status of 0 or 1

• Patients must have a complete physical examination and medical history within 28 days prior to step 2 randomization

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets >= 75,000/mcL

• Hemoglobin >= 9 g/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 5 x institutional upper limit of normal (IULN)

• Bilirubin =< 1.5 mg/dL

• Calculated creatinine clearance > 30 ml/min within 14 days prior to step 2 randomization

• Patients who have had an echocardiogram performed within 6 months prior to step 2 randomization must have ventricular ejection fraction (left ventricular ejection fraction [LVEF]) >= 50% or >= within normal limits for the institution

• Patients must not have an uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, severe infection, severe malnutrition, unstable angina, class III-IV New York Heart Association (NYHA) congestive heart failure, ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within 6 months prior to step 2 randomization

• Patients must not have any known previous or concurrent condition suggesting susceptibility to hypersensitivity or allergic reactions, including, but not limited to: known hypersensitivity to any of the study treatments or to excipients of recombinant human or humanized antibodies; patients with mild or seasonal allergies may be included after discussion with the study chairs

• Patients must not be planning treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocol-specified anti-cancer therapy including concurrent investigational agents of any type

• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade lesions such as incidental appendix carcinoid, or any other cancer from which the patient has been disease and treatment free for two years; prostate cancer patients on active surveillance are eligible

• Patients must not be pregnant or nursing; females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method while on study and for at least 7 months after the last dose of study treatment; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• Patients must be given the opportunity to consent to the optional submission of tissue for future research

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; the appropriate consent form for this registration is the step 2 consent form

• STEP 2 RANDOMIZATION: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Patients must have documented disease progression while on CETIRI (Arm 2) on this protocol; the Follow-up Tumor Assessment Form documenting disease progression must be submitted to Southwest Oncology Group (SWOG) prior to step 3 crossover registration; registration to step 3 crossover must be within 28 days of discontinuation of CETIRI protocol treatment; patients going off treatment for any other reason are not eligible

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Patients must have a Zubrod performance status of 0 or 1

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): ANC >= 1,500/mcL

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Platelets >= 75,000/mcL

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Hemoglobin >= 9 g/dL

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): AST and ALT both =< 5 x institutional upper limit of normal (IULN)

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Bilirubin =< 1.5 mg/dL

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Calculated creatinine clearance > 30 ml/min within 14 days prior to step 3 crossover registration

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Patients must have left ventricular ejection fraction (LVEF) >= 50% or >= lower limit of normal for the institution by echocardiogram within 14 days prior to step 3 crossover registration

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Patients must have a magnesium, potassium, calcium, sodium, bicarbonate, and chloride performed within 14 days prior to step 3 crossover registration

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; the appropriate consent form for this registration is the step 2 consent form

• STEP 3 CROSSOVER REGISTRATION (OPTIONAL): As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Colon Adenocarcinoma
• Colonic Neoplasms
• ERBB2 Gene Amplification
• Rectal Adenocarcinoma
• Rectal Neoplasms
• Recurrence
• Recurrent Colon Carcinoma
• Recurrent Rectal Carcinoma
• Stage III Colon Cancer AJCC v7
• Stage III Rectal Cancer AJCC v7
• Stage IIIA Colon Cancer AJCC v7
• Stage IIIA Rectal Cancer AJCC v7
• Stage IIIB Colon Cancer AJCC v7
• Stage IIIB Rectal Cancer AJCC v7
• Stage IIIC Colon Cancer AJCC v7
• Stage IIIC Rectal Cancer AJCC v7
• Stage IV Colon Cancer AJCC v7
• Stage IV Rectal Cancer AJCC v7
• Stage IVA Colon Cancer AJCC v7
• Stage IVA Rectal Cancer AJCC v7
• Stage IVB Colon Cancer AJCC v7
• Stage IVB Rectal Cancer AJCC v7

Intervention

Biological:
• Cetuximab
Given IV

Drug:
• Irinotecan Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Pertuzumab
Given IV
• Trastuzumab
Given IV

Device:
• HER-2 testing
Central testing of HER-2 for eligibility

Locations

Country	Name	City	State
Puerto Rico	Advance Oncology Center	Aguadilla
Puerto Rico	Doctor's Cancer Center-Arecibo	Arecibo
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Hematologia Oncologia San Pablo	Bayamon
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Instituto Oncologia Moderna Ponce	Ponce
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	Primary Care Physician Group	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
Puerto Rico	Centro de Hematologia y Oncologia del Sur	Santa Isabel
United States	Hawaii Cancer Care - Savio	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Hickman Cancer Center	Adrian	Michigan
United States	Riverwood Healthcare Center	Aitkin	Minnesota
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Saint Anthony's Health	Alton	Illinois
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	University of Colorado Hospital	Aurora	Colorado
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Houston Methodist San Jacinto Hospital	Baytown	Texas
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Overlake Medical Center	Bellevue	Washington
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Beverly Hospital	Beverly	Massachusetts
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	McLaren Cancer Institute-Bloomfield	Bloomfield	Michigan
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Boulder Community Foothills Hospital	Boulder	Colorado
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	United Hospital Center	Bridgeport	West Virginia
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	AtlantiCare Health Park-Cape May Court House	Cape May Court House	New Jersey
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Atrium Health University City/LCI-University	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina
United States	Levine Cancer Institute-SouthPark	Charlotte	North Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Coffeyville Regional Medical Center	Coffeyville	Kansas
United States	Main Line Health Center-Collegeville	Collegeville	Pennsylvania
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Baptist Health Corbin	Corbin	Kentucky
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	City of Hope Corona	Corona	California
United States	UC Irvine Health Cancer Center-Newport	Costa Mesa	California
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa
United States	Jennie Edmundson Memorial Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Sutter Davis Hospital	Davis	California
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Colorado at Sloan's Lake	Denver	Colorado
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Denver Health Medical Center	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Epic Care-Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	AtlantiCare Surgery Center	Egg Harbor Township	New Jersey
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Rocky Mountain Cancer Centers - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	The Melanoma and Skin Cancer Institute	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Main Line Health Center-Exton	Exton	Pennsylvania
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Levine Cancer Institute - Rutherford	Forest City	North Carolina
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	CaroMont Regional Medical Center	Gastonia	North Carolina
United States	Levine Cancer Institute-Gaston	Gastonia	North Carolina
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Smilow Cancer Hospital Care Center at Glastonbury	Glastonbury	Connecticut
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Grand Valley Oncology	Grand Junction	Colorado
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Wayne Hospital	Greenville	Ohio
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Smilow Cancer Hospital Care Center - Guiford	Guilford	Connecticut
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	21st Century Oncology-Henderson	Henderson	Nevada
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Houston Methodist Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Methodist Willowbrook Hospital	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Vidant Oncology-Kenansville	Kenansville	North Carolina
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Franciscan Saint Elizabeth Health - Lafayette East	Lafayette	Indiana
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	City of Hope Antelope Valley	Lancaster	California
United States	Fairfield Medical Center	Lancaster	Ohio
United States	McLaren-Greater Lansing	Lansing	Michigan
United States	Mid-Michigan Physicians-Lansing	Lansing	Michigan
United States	Sparrow Hospital	Lansing	Michigan
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	21st Century Oncology	Las Vegas	Nevada
United States	21st Century Oncology-Fort Apache	Las Vegas	Nevada
United States	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Atrium Health Lincoln/LCI-Lincolnton	Lincolnton	North Carolina
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Saint Joseph London	London	Kentucky
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Jewish Hospital	Louisville	Kentucky
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Baptist Health Madisonville/Merle Mahr Cancer Center	Madisonville	Kentucky
United States	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Middlesex Hospital	Middletown	Connecticut
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	City of Hope Mission Hills	Mission Hills	California
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Atrium Health Union/LCI-Union	Monroe	North Carolina
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire
United States	Baptist Health Floyd	New Albany	Indiana
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Bryn Mawr Health Center	Newtown Square	Pennsylvania
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Sutter Cancer Research Consortium	Novato	California
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Integris Cancer Institute of Oklahoma	Oklahoma City	Oklahoma
United States	Integris Southwest Medical Center	Oklahoma City	Oklahoma
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Baptist Health Paducah	Paducah	Kentucky
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Lahey Medical Center-Peabody	Peabody	Massachusetts
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Vidant Oncology-Richlands	Richlands	North Carolina
United States	Reid Health	Richmond	Indiana
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Riverton Hospital	Riverton	Utah
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Scott and White Healthcare Round Rock	Round Rock	Texas
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Mills Health Center	San Mateo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	City of Hope - Santa Clarita	Santa Clarita	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Low Country Cancer Care	Savannah	Georgia
United States	Summit Cancer Care-Candler	Savannah	Georgia
United States	Community Medical Center	Scranton	Pennsylvania
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Atrium Health Cleveland/LCI-Cleveland	Shelby	North Carolina
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Johnston Memorial Hospital	Smithfield	North Carolina
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	South Jordan Health Center	South Jordan	Utah
United States	City of Hope South Pasadena	South Pasadena	California
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Union Hospital	Terre Haute	Indiana
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC-Upper Valley	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Kent Hospital	Warwick	Rhode Island
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	AdventHealth Infusion Center Weaverville	Weaverville	North Carolina
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	City of Hope West Covina	West Covina	California
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Winchester Hospital	Winchester	Massachusetts
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival(PFS)	To evaluate the efficacy of trastuzumab and pertuzumab (TP) in HER-2 amplified metastatic colorectal cancer (mCRC) by comparing progression-free survival (PFS) on TP compared to control arm of cetuximab and irinotecan (CETIRI). Progression-free survival is defined as the time from date of randomization to date of first documentation of progression. Using RECIST 1.1, progression is defined as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician, appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration (defined as, global deterioration of health status requiring discontinuation of treatment without objective evidence of progression), or death due to any cause.	Up to 3 years post randomization
Secondary	Overall Response Rate (ORR) for TP and CETIRI Treatment Arms	To evaluate the overall response rate (ORR), including confirmed complete and partial response per RECIST 1.1, in the TP and CETIRI treatment arms. Overall response rate includes complete response(CR) and partial response(PR). Complete response is defined as complete disappearance of all target and non-target lesions and no related symptoms. Partial response is defined as a greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions for patients with at least one measurable lesion.	From baseline, through duration of treatment (once per cycle while on treatment), and every 8 weeks after treatment until progression, up to 3 years after the last accrual to registration step 2
Secondary	2 Year Overall Survival (OS) for TP and CETIRI Treatment Arms	Percentage of participants still alive 2 years after the last accrual to registration step 2. Overall survival is defined as time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date.	from the date of the last accrual to registration step 2 to date of death due to any cause, up to 2 years
Secondary	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs.	Routine toxicities were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, and SAEs were evaluated according to CTCAE version 5.0. Only adverse events that are possibly, probably, or definitely related to study drug are reported.	Duration of treatment and follow-up until death or 3 years post Step 2 Randomization.