Testing the Use of Targeted Treatment for RET Positive Advanced Non-small Cell Lung Cancer

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title:

A Randomized Phase II Study of Carboplatin and Pemetrexed w/ or w/o Selpercatinib in Participants With Non-Squamous RET Fusion-Positive Stage IV Non-Small Cell Lung Cancer and Progression of Disease on Prior RET Directed Therapy (Lung-MAP Sub-Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05364645
• Other study ID #: S1900F
• Secondary ID: NCI-2022-02517S1
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2022
• Est. completion date: May 1, 2029

Study information

• Verified date: February 2023
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II Lung-MAP treatment trial tests whether carboplatin and pemetrexed with or without selpercatinib works to shrink tumors in patients with RET fusion-positive non-small cell lung cancer that is stage IV or has not responded to previous RET directed therapy. Chemotherapy drugs, such as carboplatin and pemetrexed, 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. Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib in combination with carboplatin and pemetrexed may help lower the chance of the cancer growing and spreading.

Description:

PRIMARY OBJECTIVE: I. To compare investigator-assessed progression-free survival (IA-PFS) in participants with RET fusion-positive non-small cell lung cancer (NSCLC) with acquired selective RET inhibitor resistance randomized to carboplatin and pemetrexed with or without selpercatinib. SECONDARY OBJECTIVES: I. To evaluate if the combination of selpercatinib combined with carboplatin and pemetrexed during the first cycle of treatment has an acceptable toxicity rate. II. To evaluate the frequency and severity of toxicities within the arms. III. To compare the investigator-assessed objective response rate (ORR) (complete or partial confirmed response) between the arms. IV. To compare overall survival (OS) between the arms. V. To evaluate duration of investigator-assessed response among responders within each treatment arm. 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 participants with refractory non-small cell lung cancer (NSCLC). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive carboplatin intravenously (IV) over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also selpercatinib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients who had disease progression are followed up every 6 months for 2 years and then at 3 years. Patients who did not have disease progression are followed up every 12 weeks until disease progression.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: May 1, 2029
• Est. primary completion date: May 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must have stage IV or recurrent disease
• Participants must have been assigned to S1900F based on biomarker analysis of tissue

and/or blood and determined to have RET fusion-positive NSCLC as defined here:

• Participants must have RET fusion-positive NSCLC as determined by the Foundation Medicine (FMI) tissue-assay or other tumor-based assays such as next generation sequencing (NGS), polymerase chain reaction (PCR), or fluorescent in situ hybridization (FISH), or by cfDNA blood assay as outlined in the LUNGMAP Screening Protocol. Participants previously tested for and determined to have RET-fusion-positive NSCLC outside of LUNGMAP, must also submit tissue for central FMI testing on the LUNGMAP Screening Protocol. Participants with RET fusions detected by 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
• Participants must be negative for all additional validated oncogenic drivers that could cause resistance to selpercatinib treatment. This includes EGFR sensitizing mutations, EGFR T790M mutations, ALK gene fusions, ROS1 gene fusion, KRAS activating mutations, BRAF V600E mutation and MET exon 14 skipping mutations 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 randomization.
• Participants 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 randomization. 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 randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants 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 randomization
• Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study randomization
• Participants must have received and developed disease progression during or after an anti-RET inhibitors treatment. The anti-RET inhibitor therapy must be the most recent therapy
• Participants must have progressed (in the opinion of the treating physician) following the most recent line of therapy
• Participants must have recovered (=< grade 1) from any side effects of prior therapy. Participants must not have received any radiation therapy within 14 days prior to sub-study randomization
• For participants with stage IV or recurrent disease, the participant must not have received a platinum-based chemotherapy regimen. For participants whose prior systemic therapy was for stage I-III disease only (i.e., participant has not received any treatment for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must not have occurred within one year (365 days) from the last date that the participant received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in combination (e.g., nivolumab, pembrolizumab, or durvalumab) is allowed
• Participants must have an electrocardiogram (ECG) performed within 28 days prior to sub-study randomization. It is suggested that a local cardiologist review the corrected QT by Fridericia's correction formula (QTcF) intervals
• Absolute neutrophil count (ANC) >= 1.5 x 10^3/uL obtained within 28 days prior to sub-study randomization
• Platelet count >= 100 x 10^3/uL obtained within 28 days prior to sub-study randomization
• Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study randomization
• Serum bilirubin =< institutional upper limit of normal (IULN) and either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to sub-study randomization (if both ALT and AST are done, both must be < 2 x IULN). For participants 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)
• Participants must have a serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study randomization
• Participants must have Zubrod performance status 0-1 documented within 28 days prior to sub-study randomization
• Participants must provide pre-study history and physical exam within 28 days prior to sub-study randomization
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study randomization
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to sub-study randomization
• Participants 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 sub-study randomization
• Participants must be able to swallow capsules
• Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
• Participants must also be offered participation in banking and in the correlative studies for collection and future use of specimens
• Participants 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)
• Participants 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

Exclusion Criteria:

• Participants 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 sub-study randomization, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study randomization
• Participants must not have received any prior systemic therapy (systemic chemotherapy, tyrosine kinase inhibitor [TKI], immunotherapy or investigational drug) within 14 days prior to sub-study randomization
• Participants 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
• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not have had a major surgery within 14 days prior to sub-study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
• Participants must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., participants 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
• Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Lung Non-Small Cell Carcinoma
• 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:
• Carboplatin
Given IV
• Pemetrexed
Given IV
• Selpercatinib
Given PO

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	UPMC Altoona	Altoona	Pennsylvania
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	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Advocate Good Shepherd Hospital	Barrington	Illinois
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	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	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	UPMC Hillman Cancer Center at Butler Health System	Butler	Pennsylvania
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	UPMC Camp Hill	Camp Hill	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	WellSpan Medical Oncology and Hematology	Chambersburg	Pennsylvania
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UPMC Hillman Cancer Center - Passavant - Cranberry	Cranberry Township	Pennsylvania
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	UPMC Western Maryland	Cumberland	Maryland
United States	Carle on Vermilion	Danville	Illinois
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
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	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
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	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Oncology Hematology Associates	Greenville	Pennsylvania
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	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	IRMC Cancer Center	Indiana	Pennsylvania
United States	Kaiser Permanente-Irvine	Irvine	California
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	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	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	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Sparrow Hospital	Lansing	Michigan
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
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	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
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	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	UPMC Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	UPMC Hillman Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Arnold Palmer Cancer Center Medical Oncology Norwin	N. Huntingdon	Pennsylvania
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	UPMC Hillman Cancer Center - New Castle	New Castle	Pennsylvania
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Kaiser Permanente-Ontario	Ontario	California
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
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	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Mercy Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Kaiser Permanente-Riverside	Riverside	California
United States	University of Rochester	Rochester	New York
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	Saint Helena Hospital	Saint Helena	California
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
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	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
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	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Trinity's Tony Teramana Cancer Center	Steubenville	Ohio
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
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	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
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	UPMC Cancer Center-Uniontown	Uniontown	Pennsylvania
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
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	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	AdventHealth Infusion Center Weaverville	Weaverville	North Carolina
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	UPMC West Mifflin-Cancer Center Jefferson	West Mifflin	Pennsylvania
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	UPMC Memorial	York	Pennsylvania
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-assessed progression-free survival (PFS)	Will be compared between the arms using a 1-sided log-rank test at the 0.10 level upon the observation of 55 PFS events or at a maximum follow-up duration (from closure of accrual of 15 months). Will be estimated using the method of Kaplan-Meier. Confidence intervals about median event times will be estimated using the Brookmeyer-Crowley method. For point estimates at landmark times, the associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression.	From date of sub-study randomization 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
Secondary	Incidence of grade 3 or higher non hematologic toxicity and grade 4 or higher hematologic toxicity		During first cycle (1 cycle = 21 days)
Secondary	Frequency and severity of adverse events		Up to 3 years
Secondary	Investigator-assessed objective response rate		Up to 3 years
Secondary	Overall survival	Will be estimated using the method of Kaplan-Meier. Confidence intervals about median event times will be estimated using the Brookmeyer-Crowley method. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression.	From date of sub-study randomization to date of death due to any cause, assessed up to 3 years
Secondary	Duration of investigator-assessed response	Will be estimated using the method of Kaplan-Meier. Confidence intervals about median event times will be estimated using the Brookmeyer-Crowley method. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios for these outcomes will be estimated using a Cox Proportional Hazards regression.	From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression, or death due to any cause among participants who achieve a response (CR or PR), assessed up to 3 years