Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial)

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title:

A Phase II Study of LOXO-292 in Patients With RET Fusion-Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP Sub-Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04268550
• Other study ID #: S1900B
• Secondary ID: NCI-2019-08097S1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 8, 2020
• Est. completion date: January 1, 2025

Study information

• Verified date: December 2023
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II LUNG-MAP treatment trial studies how well selpercatinib works in treating patients with RET fusion-positive non-small cell lung cancer that is stage IV or has come back (recurrent). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVE:

I. To evaluate the objective response rate (ORR) (confirmed complete or partial response) by blinded independent centralized review (BICR) associated with selpercatinib (LOXO-292) in patients with previously-treated stage IV or recurrent RET fusion-positive non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate the duration of BICR-assessed response among BICR responders. II. To evaluate the frequency and severity of toxicities. III. To evaluate the investigator-assessed objective response rate (confirmed complete or partial response).

IV. To evaluate duration of investigator-assessed response among patients with a response as determined by the local investigator.

V. To evaluate investigator-assessed progression-free survival (IA-PFS). VI. To evaluate BICR-assessed PFS. VII. To evaluate overall survival (OS).

VIII. Among patients with brain metastases at baseline:

VIIIa. To evaluate the central nervous system (CNS) response rate (confirmed complete response [CR]).

VIIIb. To evaluate the duration of intracranial response among patients with a CNS response.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at baseline, progression, and end of treatment for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA).

II. To establish a tissue/blood repository from patients with refractory non-small cell lung cancer (NSCLC).

OUTLINE:

Patients receive selpercatinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then at the end of 3 years from date of sub-study registration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients must have been assigned to S1900B based on biomarker analysis of tissue and/or blood and determined to have RET fusion-positive NSCLC as defined here:

• Patients must have RET fusion-positive NSCLC as determined by the Foundation Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected by immunohistochemistry (IHC) alone are not eligible. The testing must be done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO/International Electrotechnical Commission (IEC), College of American Pathologists (CAP), or similar certification. Presence of RET fusions detected on tests performed outside of LUNGMAP must have been confirmed by the study biomarker review panel

• For patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen. For patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed

• Patients must be negative for all additional validated oncogenic drivers that could cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E mutation and MET exon 14 skipping mutation or high-level amplification and expression

• Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP screening/pre-screening FoundationOne test. If prior data is not available, results from the FMI testing must be obtained prior to sub-study registration

• Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration. CT and MRI scans must be submitted for central review via transfer of images and data (TRIAD)

• Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to sub-study registration

• Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration

• Patients with known human immunodeficiency virus (HIV) infection are eligible, provided they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration

• Patients must be able to swallow capsules

• Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy

• Patients must have recovered (=< grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration

• Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to sub-study registration)

• Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study registration)

• Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x IULN

• Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN (within 28 days prior to sub-study registration) (if both ALT and AST are done, both must be =< 2 IULN). For patients with liver metastases, bilirubin and either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

• Serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula (within 28 days prior to sub-study registration)

• Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration

• Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Patients must have electrolytes and blood urea nitrogen (BUN) performed within 14 days prior to sub-study registration

• Patients must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)

• Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens

• 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

• 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

• Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)

Exclusion Criteria:

• Patients must not have received any prior treatment with selective anti-RET inhibitors (anti-RET multikinase inhibitors are permitted)

• Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration

• Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 14 days prior to sub-study registration

• Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable

• Patient must not have had a major surgery within 14 days prior to sub-study registration. Patient must have fully recovered from the effects of prior surgery in the opinion of the treating investigator

• Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia

• Patients must not have a QT interval by Fridericia (QTcF) > 470 msec based on the electrocardiogram (ECG) within 28 days prior to registration. It is suggested that a local cardiologist review the QTcF intervals

• Patients must not have any clinically significant uncontrolled systemic illness, including but not limited to uncontrolled infection, requiring intravenous antibiotics, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus

• Uncontrolled diabetes: Patients who have a diagnosis of diabetes must have an hemoglobin (Hb) A1C < 7% within 28 days prior to registration. The same criterion will be used in patients with confirmed diagnosis of diabetes mellitus who have been on a stable dietary or therapeutic regimen for this condition in the last three months

• Uncontrolled blood pressure and hypertension: All blood pressure measurements within the 28 days prior to registration must be systolic blood pressure (SBP) =< 180 and diastolic blood pressure (DBP) =< 100. An exception can be made by a healthcare provider for a patient with a single blood pressure elevation who upon rechecking has a blood pressure within the parameters above

• Patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of LOXO-292 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or active peptic ulcer disease)

• Patients must not be planning to receive any strong inhibitors or inducers of CYP3A4 at least 14 days prior to sub-study registration and throughout protocol treatment

• Patients must not be planning to use proton pump inhibitors (PPIs) at least one week prior to sub-study registration and throughout protocol treatment

• Patients must not be pregnant or nursing. Women study patients of reproductive potential and fertile men study patients and their partners must abstain or use effective contraception (including barrier method) while receiving study treatment and for at least 3 months after the last dose of LOXO-292. Male study patients must agree not to donate sperm for 6 months after the last dose of LOXO-292. 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

Intervention

Drug:
• Selpercatinib
Given PO

Locations

Country	Name	City	State
United States	Hawaii Cancer Care - Savio	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
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	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northside Hospital	Atlanta	Georgia
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	University of Colorado Hospital	Aurora	Colorado
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Waldo County General Hospital	Belfast	Maine
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	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Northeast Georgia Medical Center Braselton	Braselton	Georgia
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	James J Peters VA Medical Center	Bronx	New York
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
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	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rex Hematology Oncology Associates-Cary	Cary	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
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	Memorial Hospital North	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	The Mark H Zangmeister Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Western Maryland Regional Medical Center	Cumberland	Maryland
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Genesis Cancer Care Institute	Davenport	Iowa
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Iowa Cancer Specialists	Davenport	Iowa
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Northside Hospital - Duluth	Duluth	Georgia
United States	Durham VA Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Fox Chase Cancer Center - East Norriton Hospital Outpatient Center	East Norriton	Pennsylvania
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
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	Kaiser Permanente-Fontana	Fontana	California
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Rex Hematology Oncology Associates-Garner	Garner	North Carolina
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North 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 Cancer Institute - Greer	Greer	South Carolina
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
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	HaysMed University of Kansas Health System	Hays	Kansas
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	Hawaii Cancer Care Inc-POB II	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	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	West Michigan Cancer Center	Kalamazoo	Michigan
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	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Sparrow Hospital	Lansing	Michigan
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at Oakey	Las Vegas	Nevada
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
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	Loma Linda University Medical Center	Loma Linda	California
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	UCHealth Lone Tree Health Center	Lone Tree	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Bayhealth Hospital Sussex Campus	Milford	Delaware
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	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Licking Memorial Hospital	Newark	Ohio
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
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	Kaiser Permanente-Ontario	Ontario	California
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
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	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Rex Cancer Center	Raleigh	North Carolina
United States	Rex Cancer Center of Wakefield	Raleigh	North Carolina
United States	Rex Hematology Oncology Associates-Blue Ridge	Raleigh	North Carolina
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Renown Regional Medical Center	Reno	Nevada
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Kaiser Permanente-Riverside	Riverside	California
United States	University of Rochester	Rochester	New York
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Sutter Roseville Medical Center	Roseville	California
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	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	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Salem Hospital	Salem	Oregon
United States	Salina Regional Health Center	Salina	Kansas
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 Marcos	San Marcos	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Genesis Cancer Center - Silvis	Silvis	Illinois
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	Suburban Hematology Oncology Associates - Snellville	Snellville	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Prisma Health Cancer Institute - Spartanburg	Spartanburg	South Carolina
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Moffitt Cancer Center	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Virtua Voorhees	Voorhees	New Jersey
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Veterans Affairs Connecticut Healthcare System-West Haven Campus	West Haven	Connecticut
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Metro Health Hospital	Wyoming	Michigan
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
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)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate by blinded independent centralized review (BICR)	A response will be confirmed by a complete response (CR) or partial response (PR). Proportions and associated confidence intervals will be calculated.	Up to 3 years from date of sub-study registration
Secondary	Incidence of adverse events	Will be assessed using Common Terminology Criteria for Adverse Event version 5.0.	Up to 3 years from date of sub-study registration
Secondary	BICR-progression-free survival (PFS)	Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times	From date of sub-study registration to date of first documentation of progression assessed by BICR or symptomatic deterioration, or death due to any cause, assessed up to 3 years from date of sub-study registration
Secondary	Investigator-assessed (IA) PFS	Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times	From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years from date of sub-study registration
Secondary	Overall survival	Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times	Up to 3 years from date of sub-study registration
Secondary	BICR-duration of response (DOR)	Will be evaluated among patients who achieve a confirmed response. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times. The median DOR and percentage with DOR at landmark times at 6 and 12 months after documentation of confirmed response will be estimated.	From date of first documentation of confirmed response (CR or PR) to date of first documentation of progression assessed by BICR or symptomatic deterioration, or death due to any cause among patients who achieve, assessed at 6 and 12 months
Secondary	Central nervous system (CNS) response rate	Will be assessed among patients with brain metastases. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times	Baseline
Secondary	Duration of intracranial response among patients with a CNS response	Will be assessed among patients with brain metastases. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to estimate confidence intervals for the median using Greenwood's formula and based on a log-log transformation applied on the survival function for landmark times	Baseline