Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced Breast Cancer

Stage IIIC Breast Cancer AJCC v7 Clinical Trial

Official title:

A Randomized Phase III Trial Evaluating Pathologic Complete Response Rates in Patients With Hormone Receptor-Positive, HER2-Positive, Large Operable and Locally Advanced Breast Cancer Treated With Neoadjuvant Therapy of Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP) With or Without Estrogen Deprivation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02003209
• Other study ID #: NCI-2013-02228
• Secondary ID: NCI-2013-02228NS
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 15, 2014
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies docetaxel, carboplatin, trastuzumab, and pertuzumab with estrogen deprivation to see how they work compared to docetaxel, carboplatin, trastuzumab, and pertuzumab without estrogen deprivation in treating patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that is operable or has spread from where it started to nearby tissue or lymph nodes (locally advanced). Drugs used in chemotherapy, such as docetaxel, carboplatin, trastuzumab, and pertuzumab, 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 more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using goserelin acetate and aromatase inhibition therapy may fight breast cancer by blocking the use of estrogen by the tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. Giving combination chemotherapy and radiation therapy with or without hormone therapy may be an effective treatment for hormone receptor-positive, HER2-positive, operable or locally advanced breast cancer.

Description:

PRIMARY OBJECTIVES:

I. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of therapy of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) yields a greater rate of pathologic complete response (pCR) (breast and nodes) than TCHP alone when administered to women with operable, hormone receptor-positive, HER2-positive breast cancer.

SECONDARY OBJECTIVES:

I. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP will increase the pCR rate in the breast compared to TCHP alone when administered to women with operable, hormone receptor-positive, HER2-positive breast cancer.

II. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP improves recurrence-free interval (RFI) in women with operable, hormone receptor-positive, HER2-positive breast cancer.

III. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP improves overall survival (OS) in women with operable, hormone receptor-positive, HER2-positive breast cancer.

IV. To compare the rates of second primary invasive cancer by treatment arm. V. Assessment of patterns of pCR, RFI, and OS by menopausal status. VI. To evaluate the cardiac toxicity associated with each of the regimens. VII. To compare the effect of adding estrogen deprivation to neoadjuvant therapy on endocrine-related symptoms in all patients by treatment arm.

VIII. To compare the effect of adding estrogen deprivation to neoadjuvant therapy on vasomotor symptoms, musculoskeletal, and vaginal complaints as well as quality of life.

IX. To determine a relationship between pCR and a potential mechanism of resistance/sensitivity in hormone receptor-positive, HER2-positive tumors.

X. To evaluate tumor infiltrating lymphocytes (TILs) and immune biomarkers as predictors of pCR.

XI. To study early changes in TILs and other immune biomarkers in response to TCHP.

OUTLINE: Patients are randomized to 1 of 2 treatments arms.

NEOADJUVANT:

ARM I: Patients receive docetaxel intravenously (IV) over 60 minutes, carboplatin IV over 30-60 minutes, trastuzumab IV over 30-90 minutes, and pertuzumab IV over 30-60 on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment.

ARM II: All patients receive docetaxel, carboplatin, trastuzumab, and pertuzumab as in arm I. Premenopausal patients also receive goserelin acetate subcutaneously (SC) every 28 days until surgery and aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Postmenopausal patients receive aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment.

SURGERY: Patients undergo lumpectomy or mastectomy.

RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery.

ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year.

After completion of study treatment, patients are followed up every 6, 9, 12, and 18 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 315
• Est. completion date: December 31, 2024
• Est. primary completion date: October 31, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer; (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer)

• Women of reproductive potential must agree to use an effective non-hormonal method of contraception during study therapy (chemotherapy, trastuzumab, pertuzumab, and estrogen deprivation therapy) and for at least 7 months after the last dose of study therapy

• Submission of tumor samples is required for all patients; the local pathology department policy regarding release of tumor samples must be considered in the screening process; patients whose tumor samples are located in a pathology department that by policy will not submit any samples for research purposes should not be approached for participation in the B-52 trial

• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines

• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Clinical staging for the primary tumor can be cT1c (must be 2.0 cm) or T2-T4 if clinically node negative; if the regional lymph nodes are cN1 and cytologically or histologically positive or if cN2-N3 with or without a biopsy, the primary breast tumor can be cT0-T4

• The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy

• Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or magnetic resonance imaging [MRI]) within 6 weeks prior to randomization; if suspicious or abnormal, fine needle aspirate (FNA) or core biopsy is recommended, also within 6 weeks prior to randomization; findings of these evaluations will be used to determine the nodal status prior to randomization:

• Nodal status - negative

• Imaging of the axilla is negative

• Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative

• Nodal status - positive

• FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive

• Imaging is suspicious or abnormal but FNA or core biopsy was not performed

• Patients may be premenopausal or postmenopausal at the time of randomization; for study purposes, postmenopausal is defined as:

• Age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or

• Age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or

• Documented bilateral oophorectomy

• The tumor must have been determined to be HER2-postive as follows:

• Immunohistochemistry (IHC) 3+ or

• In situ hybridization (ISH)-positive (defined by ratio of HER2 to circulating endothelial progenitors [CEP]17 >= 2.0 or HER2 gene copy number >= 6 per nucleus)

• The tumor must have been determined to be estrogen receptor (ER) and/or progesterone (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline recommendations for hormone receptor testing; patients with >= 1% ER or PgR staining by IHC are considered positive

• Absolute neutrophil count (ANC) must be >= 1200/mm^3

• Platelet count must be >= 100,000/mm^3

• Hemoglobin must be >= 10 g/dL

• Total bilirubin must be =< upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin

• Alkaline phosphatase must be =< 2.5 x ULN for the lab

• Aspartate aminotransferase (AST) must be =< 1.5 x ULN for the lab

• Alkaline phosphatase and AST may not both be > the ULN; for example, if the alkaline phosphatase is > the ULN but =< 2.5 x ULN, the AST must be =< the ULN; if the AST is > the ULN but =< 1.5 x ULN, the alkaline phosphatase must be =< ULN; Note: If alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be =< 1.5 x ULN; if both were performed, the AST must be =< 1.5 x ULN

• Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], MRI, positron emission tomography [PET]-CT, or PET scan) performed within 6 weeks prior to randomization does not demonstrate metastatic disease and the requirements are met

• Patients with alkaline phosphatase that is > ULN but =< 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 6 weeks prior to randomization does not demonstrate metastatic disease

• Within 6 weeks prior to randomization, the most recent serum creatinine must be =< ULN or measured or calculated creatinine clearance must be > 60 mL/min

• Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; (LVEF assessment performed by 2-dimensional [2-D] echocardiogram is preferred; however, multi gated acquisition scan [MUGA] scan may be substituted based on institutional preferences); the LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal; note: since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment; if the baseline LVEF is > 65%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain

Exclusion Criteria:

• FNA alone to diagnose the breast cancer

• Excisional biopsy or lumpectomy performed prior to randomization

• Surgical axillary staging procedure prior to randomization; pre-neoadjuvant therapy sentinel node biopsy is not permitted

• Definitive clinical or radiologic evidence of metastatic disease; (chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 90 days prior to randomization)

• Synchronous bilateral invasive breast cancer

• Synchronous or previous contralateral invasive breast cancer; (patients with synchronous and/or previous contralateral ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] are eligible)

• Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS; (patients with synchronous or previous ipsilateral LCIS are eligible)

• Treatment including radiation therapy (RT), chemotherapy, targeted therapy, or endocrine therapy for the currently diagnosed breast cancer prior to randomization

• Previous endocrine therapy such as raloxifene or tamoxifen (or other selective estrogen receptor modulator [SERM]) or an aromatase inhibitor for any malignancy

• Previous therapy with anthracycline, taxanes, carboplatin, trastuzumab, or other HER2 targeted therapies for any malignancy

• Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (these patients are eligible if this therapy is discontinued prior to randomization)

• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization

• Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens; this includes but is not confined to:

• Active cardiac disease:

• Angina pectoris that requires the use of anti-anginal medication;

• Ventricular arrhythmias except for benign premature ventricular contractions;

• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;

• Conduction abnormality requiring a pacemaker;

• Valvular disease with documented compromise in cardiac function; and

• Symptomatic pericarditis

• History of cardiac disease:

• Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;

• History of documented congestive heart failure (CHF); and

• Documented cardiomyopathy

• Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)

• Active hepatitis B or hepatitis C with abnormal liver function tests

• Intrinsic lung disease resulting in dyspnea

• Poorly controlled diabetes mellitus

• Active infection or chronic infection requiring chronic suppressive antibiotics

• Patients known to be human immunodeficiency virus (HIV) positive with a baseline cluster of differentiation (CD)4 count of < 250 cells/mm^3 or have a history of acquired immune deficiency syndrome (AIDS) indicator conditions; patients taking anti-retroviral therapy that may have a potential overlapping toxicity with the study therapy are not eligible

• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2, per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

• Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function

• Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up

• Conditions that would prohibit administration of corticosteroids

• Chronic daily treatment with corticosteroids with a dose of >= 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)

• Known hypersensitivity to any of the study drugs or any of the ingredients or excipients of these drugs (e.g., polysorbate 80), including sensitivity to benzyl alcohol

• Pregnancy or lactation at the time of study entry; (note: pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)

• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements

• Use of any investigational product within 30 days prior to randomization

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Stage IB Breast Cancer AJCC v7
• Stage IIA Breast Cancer AJCC v6 and v7
• Stage IIB Breast Cancer AJCC v6 and v7
• Stage IIIA Breast Cancer AJCC v7
• Stage IIIB Breast Cancer AJCC v7
• Stage IIIC Breast Cancer AJCC v7

Intervention

Drug:
• Aromatase Inhibition Therapy
Given at the investigator's discretion
• Carboplatin
Given IV

Other:
• Cytology Specimen Collection Procedure
Undergo 2 core biopsies

Drug:
• Docetaxel
Given IV
• Goserelin Acetate
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Pertuzumab
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Procedure:
• Therapeutic Conventional Surgery
Undergo lumpectomy or mastectomy

Biological:
• Trastuzumab
Given IV

Radiation:
• Whole Breast Irradiation
Undergo whole breast irradiation

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hospital	San Juan
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	Hendrick Medical Center	Abilene	Texas
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Hematology Oncology Associates	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	PCR Oncology	Arroyo Grande	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	University Cancer and Blood Center LLC	Athens	Georgia
United States	Northside Hospital	Atlanta	Georgia
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	Augusta University Medical Center	Augusta	Georgia
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	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Overlake Medical Center	Bellevue	Washington
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Health 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	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
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	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Presence Resurrection Medical Center	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	University of Illinois	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-Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	The Christ Hospital	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
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	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
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 Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Baptist Health Corbin	Corbin	Kentucky
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Michiana Hematology Oncology PC-Crown Point	Crown Point	Indiana
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Sutter Davis Hospital	Davis	California
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Dayton Physician LLC - Englewood	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	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
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	Colorado Blood Cancer Institute	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	Western States Cancer Research NCORP	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	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	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
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	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Easton Hospital	Easton	Pennsylvania
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus	Elizabeth	New Jersey
United States	Baptist Health Hardin	Elizabethtown	Kentucky
United States	Ascension Alexian Brothers - Elk Grove Village	Elk Grove Village	Illinois
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Saint Francis Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Saint Anne's Hospital	Fall River	Massachusetts
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Virginia Mason Federal Way Medical Center	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	Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Tidelands Georgetown Memorial Hospital	Georgetown	South Carolina
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Glens Falls Hospital	Glens Falls	New York
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
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-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kuakini Medical Center	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	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Lyndon Baines Johnson General Hospital	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	Jackson-Madison County General Hospital	Jackson	Tennessee
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Castle Medical Center	Kailua	Hawaii
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Northwest Cancer Clinic	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
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	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	Community Howard Regional Health	Kokomo	Indiana
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
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	Carolina Blood and Cancer Care Associates PA-Lancaster	Lancaster	South Carolina
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	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-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	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	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	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	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint Joseph Regional Medical Center	Lewiston	Idaho
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	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Loma Linda University Medical Center	Loma Linda	California
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	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Baptist Health Madisonville/Merle Mahr Cancer Center	Madisonville	Kentucky
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
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	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
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	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	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Garnet Health Medical Center	Middletown	New York
United States	MyMichigan Medical Center Midland	Midland	Michigan
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
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	Trinity Cancer Care Center	Minot	North Dakota
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Monongalia Hospital	Morgantown	West Virginia
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Novant Health Cancer Institute - Mount Airy	Mount Airy	North Carolina
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	El Camino Hospital	Mountain View	California
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	The Community Hospital	Munster	Indiana
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Meharry Medical College	Nashville	Tennessee
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	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Newark Radiation Oncology	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Newton Medical Center	Newton	New Jersey
United States	Sutter Cancer Research Consortium	Novato	California
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	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Capital Medical Center	Olympia	Washington
United States	Providence - Saint Peter Hospital	Olympia	Washington
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	Memorial GYN Plus	Ooltewah	Tennessee
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	AdventHealth Orlando	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Baptist Health Paducah	Paducah	Kentucky
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Midlands Community Hospital	Papillion	Nebraska
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	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	Pekin	Illinois
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	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center - Cancer Center	Pittsfield	Massachusetts
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Chilton Medical Center	Pompton	New Jersey
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Peninsula Cancer Center	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Women and Infants Hospital	Providence	Rhode Island
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	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Michigan Cancer Specialists	Roseville	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Cancer Care Associates PC	Royal Oak	Michigan
United States	Comprehensive Medical Center PLLC	Royal Oak	Michigan
United States	Hematology Oncology Consultants PC	Royal Oak	Michigan
United States	Oakland Colon Rectal Associates	Royal Oak	Michigan
United States	Oakland Medical Group	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Mercy Hospital Saint Louis	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	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
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	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Novant Health Cancer Institute - Rowan	Salisbury	North Carolina
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
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	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Christus Saint Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	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	Memorial Health University Medical Center	Savannah	Georgia
United States	Summit Cancer Care-Memorial	Savannah	Georgia
United States	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
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	Iredell Memorial Hospital	Statesville	North Carolina
United States	Novant Health Cancer Institute - Statesville	Statesville	North Carolina
United States	Mitchell Folbe MD PC	Sterling Heights	Michigan
United States	Premier Hematology Oncology Care	Sterling Heights	Michigan
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Union Hospital	Terre Haute	Indiana
United States	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Claudia BR Herke MD PC	Troy	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Hematology Oncology Consultants PC-Troy	Troy	Michigan
United States	Michigan Institute of Urology-Town Center	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	Surgical Associates Inc	Tulsa	Oklahoma
United States	Warren Clinic Oncology-Tulsa	Tulsa	Oklahoma
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Kent Hospital	Warwick	Rhode Island
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Chester County Hospital	West Chester	Pennsylvania
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Jennersville Regional Hospital	West Grove	Pennsylvania
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Ascension Saint Clare's Hospital	Weston	Wisconsin
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Novant Health Cancer Institute - Wilkesboro	Wilkesboro	North Carolina
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Winston-Salem Health Care	Winston-Salem	North Carolina
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	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes	Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy.	Up to 2.8 years (when all patients completed primary breast surgery)
Secondary	Percent of Patients With Pathologic Complete Response (pCR) in the Breast	Proportion of patients with pCR in the breast, defined as the absence of any invasive component in the resected breast specimen.	Up to 2.8 years (when all patients completed primary breast surgery)
Secondary	Recurrence Free Interval (RFI)	Kaplan-Meier estimates of the percentages of patients free from recurrence.	Time from surgery to invasive local, regional or distant recurrence, or death from breast cancer for patients with operable disease and for patients with inoperable progressive disease, assessed up to 8.4 years
Secondary	Overall Survival (OS)	Kaplan-Meier estimates of the percentages of patients surviving.	Time from randomization until death from any cause, assessed up to 8.4 years
Secondary	Rate of Second Primary Invasive Cancer of Any Type	The cumulative incidence rates of second primary cancers for the two treatment groups.	Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 8.4 years
Secondary	Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes by Menopausal Status	Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy calculated separately for premenopausal and postmenopausal women.	Up to 2.8 years (when all patients completed primary breast surgery)
Secondary	Patterns of Recurrence Free Interval (RFI) by Menopausal Status	Kaplan -Meier estimates of the percentages of patients free from recurrence by menopausal status.	Up to 5 years
Secondary	Patterns of Overall Survival (OS) by Menopausal Status	Kaplan-Meier estimates of the percentages of patients surviving by menopausal status.	Up to 5 years
Secondary	Percentage of Participants With Cardiac Toxicity Categorized According to National Cancer Institute CTCAE Version 4.0	Percentage of patients with grade 1 or higher toxicity from the Cardiac Disorders System Organ Class.	Up to 6 weeks post surgery
Secondary	Median Percentage of Tumor-infiltrating Lymphocytes (sTILS)	Percentage of Tumor-infiltrating lymphocytes present in the stroma in tissue specimen.	2.8 years
Secondary	Change in Endocrine-related Symptoms Using Breast Cancer Prevention Trial (BCPT) Symptom Checklist	Mean total score from the BCPT symptom checklist calculated as the average severity score across all items at each timepoint.	Baseline to up to 4 weeks after the last dose of chemotherapy