Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma

Unresectable Melanoma Clinical Trial

Official title:

The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04527549
• Other study ID #: EA6191
• Secondary ID: NCI-2020-04552EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: November 30, 2025

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.

Description:

PRIMARY OBJECTIVE: I. To determine the rate of one year progression-free survival (PFS) when hydroxychloroquine sulfate (hydroxychloroquine) or placebo is added to dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) in advanced BRAFV600E/K melanoma. SECONDARY OBJECTIVES: I. To compare the PFS of both arms. II. To evaluate the best overall response rate by treatment arm. III. To evaluate the complete response (CR) rate by treatment arm. IV. To evaluate the adverse event rate by treatment arm. V. To evaluate overall survival (OS) by treatment arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive dabrafenib mesylate orally (PO) twice daily (BID), trametinib dimethyl sulfoxide PO once daily (QD), and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO 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 for 1 year.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must have locally advanced unresectable stage IIIC or stage IV melanoma
• Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay
• Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline measurements of sites of disease must be obtained within 3 weeks prior to study randomization
• Patient must have been treated with prior immune checkpoint inhibitor therapy (anti PD-1 antibody, anti-CTLA-4 antibody or a combination regimen including either or both agents) either in the adjuvant or metastatic setting. Patient may have received investigational agents in combination with standard therapy, as long as it was adhering to the timeframes
• Patient must have discontinued active immunotherapy (IL-2, interferon, anti-CTLA-4 antibody, anti-PD-1 antibody etc.) or chemotherapy at least 4 weeks prior to randomization
• Patient must have discontinued any oral targeted therapy at least 2 weeks prior to randomization
• Patients must not receive any other investigational anticancer therapy during the period on study or the 4 weeks prior to randomization
• Patient may have been treated with prior adjuvant therapy including combined BRAF and MEK inhibitor therapy. Patients will be eligible if they tolerated this therapy and did not discontinue the therapy due to toxicity AND >= 6 months have elapsed since the end of adjuvant BRAF and MEK inhibition. If patients received BRAF and MEK inhibitor therapy in the metastatic setting, they are not eligible
• Patient may have been treated with prior chemotherapy or radiation therapy
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 4 months after the last dose of protocol treatment
• Patient must have recovered from clinically significant reversible toxicities from previous treatment prior to randomization. Abnormal laboratory values may be grade 1, as long as they meet the eligibility criteria
• Patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to protocol randomization)
• Platelets >= 100,000/mcL (obtained =< 14 days prior to protocol randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 14 days prior to protocol randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 14 days prior to protocol randomization)
• Creatinine =< 1.5 x institutional ULN (obtained =< 14 days prior to protocol randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patient with asymptomatic new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that CNS specific treatment is not required
• NOTE: Patient with treated brain metastases are eligible. No brain imaging is required, however, 1 week must elapse after gamma knife therapy. Patient treated with whole brain radiation that have been stable for 2 months are eligible. Patient are excluded if they have leptomeningeal disease or metastases causing spinal cord compression that are symptomatic or untreated or not stable (documented by imaging) for at least 3 months or requiring corticosteroids. Patients on a stable dose of corticosteroids for at least 1 month or who have been off of corticosteroids for at least 1 week are eligible

Exclusion Criteria:

• Patients who are known to be experiencing an objective partial response to immunotherapy at the time of study enrollment are not eligible
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patient must not have a history of interstitial lung disease (ILD) or chronic pneumonitis
• NOTE: If there is radiographic evidence of ILD that is clinically insignificant and asymptomatic, the patient would be eligible
• Patient must not have porphyria or psoriasis due to risk of disease exacerbation unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
• Patient must not have a previously documented retinal vein occlusion
• Patient must not have a history or evidence of increased cardiovascular risk

including:

• Left ventricular ejection fraction (LVEF) < institutional lower limit of normal measured within 14 days prior to randomization
• A QT interval corrected for heart rate using the Bazett's formula >= 480 msec
• Current clinically significant uncontrolled arrhythmias. Exception: Patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible
• Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram unless a cardiologist concludes the valve abnormality is not clinically significant. Patients with grade 1 abnormalities (i.e., mild regurgitation/stenosis) are eligible
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Patient with known serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety are not eligible
• Patient must not be receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents). Radiotherapy delivered to palliate pain is allowed as long as it is not targeting a lesion that meets RECIST criteria for progression. Radiation therapy to the surgical bed with gamma knife radiotherapy while on treatment during the first cycle is allowed for small volume surgically resected brain metastases. Gamma knife radiotherapy for known active, asymptomatic small volume central nervous system (CNS) lesions may be performed during the first cycle while on study. Radiotherapy for new CNS lesions identified beyond the first cycle is not allowed on study
• Patient must not have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
• Patient must not have received cytochrome P450 enzyme -inducing anticonvulsant drugs (extended-interval aminoglycoside dosing [EIADs]) (i.e. phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization
• Patient must not have a current use of a prohibited medication

Related Conditions & MeSH terms

• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Locally Advanced Melanoma
• Melanoma
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Skin Neoplasms
• Unresectable Melanoma

Intervention

Drug:
• Dabrafenib Mesylate
Given PO
• Hydroxychloroquine Sulfate
Given PO
• Placebo Administration
Given PO
• Trametinib Dimethyl Sulfoxide
Given PO

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Saint Anthony's Health	Alton	Illinois
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
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	Carle on Vermilion	Danville	Illinois
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Wayne Hospital	Greenville	Ohio
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Beebe Medical Center	Lewes	Delaware
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
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	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Dayton Physicians LLC-Upper Valley	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) rate	Estimated from the Kaplan-Meier curves and compared by treatment arm. A test statistic of the difference in one-year PFS rates divided by the square root or the sum of the variances will be used with a normal approximation. Progression will be evaluated based on international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).	From randomization to progression or death (whichever occurs first), assessed at 1 year after completion of treatment
Secondary	PFS distribution	Will be estimated using the method of Kaplan-Meier by treatment arm and compared using the log-rank test. In this analysis, all cases with PFS assessed (including cases with censored < one-year) will be included. Progression will be evaluated based on international criteria proposed by the revised RECIST guideline (version 1.1).	From randomization to progression or death (whichever occurs first), assessed at 1 year after completion of treatment
Secondary	Overall response rate	Will be estimated by treatment arm and 95% confidence intervals (CIs) will be provided. Response will be defined by the RECIST guidelines (version 1.1).	Up to 1 year after completion of treatment
Secondary	Complete response rate	Will be estimated by treatment arm and 95% CIs will be provided. Response will be defined by the RECIST guidelines (version 1.1).	Up to 1 year after completion of treatment
Secondary	Overall survival	Overall survival will be described using the method of Kaplan-Meier by treatment arm.	From randomization to death from any cause, assessed up to 1 year after completion of treatment
Secondary	Incidence of adverse events	Will be monitored carefully throughout the study and will be summarized by treatment arm. Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).	Up to 1 year after completion of treatment
Secondary	Treatment duration	Will be estimated by treatment arm.	Up to 1 year after completion of treatment