Using Biomarkers to Help Guide Safe Immunotherapy Discontinuation in Patients With Unresectable Stage IIIB-IV Melanoma, The PET-Stop Trial

Advanced Melanoma Clinical Trial

Official title:

A Phase II Study of Biomarker Driven Early Discontinuation of Anti-PD-1 Therapy in Patients With Advanced Melanoma (PET-Stop)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04462406
• Other study ID #: EA6192
• Secondary ID: NCI-2020-04463EA
• Status: Recruiting
• Phase: Phase 2
• Start date: February 9, 2021
• Est. completion date: August 29, 2026

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 biomarkers on PET/CT imaging drive early discontinuation of anti-PD-1 therapy in patients with stage IIIB-IV melanoma that cannot be removed by surgery (unresectable). Anti-PD-1 therapy has become a standard therapy option for patients with unresectable melanoma. This trial is being done to determine if doctors can safely shorten the use of standard of care anti-PD1 therapy for melanoma by using biomarkers seen on PET/CT imaging and tumor biopsy.

Description:

PRIMARY OBJECTIVE: I. To determine the 12 month event free survival (EFS) rate following discontinuation of anti-PD-1 therapy in patients with disease control and negative fludeoxyglucose F-18 (FDG)- positron emission tomography (PET)/computed tomography (CT) scan or biopsy for residual disease after 12 months of anti-PD-1 therapy (Arm A). SECONDARY OBJECTIVES: I. To determine rates of pathologic response in patients with tumor biopsies where positive hypermetabolic activity was present on FDG-PET/CT scan after 12 months of anti-PD-1 therapy (Arm B). II. To determine the overall 24 month EFS. III. To determine overall survival from start of anti-PD-1 therapy. IV. To determine percentage for patients who remain on treatment beyond 12 months because of positive FDG-PET/CT scan and positive biopsy for residual disease (or unable to obtain a biopsy). V. To determine incidence rates of treatment-related adverse events beyond 12 months from start of treatment in patients who discontinue anti-PD-1 therapy at 12 months and in patients who continue anti-PD-1 therapy beyond 12 months (Arm A versus [vs.] Arm B). EXPLORATORY OBJECTIVES: I. To assess agreement in determining FDG-PET/CT positivity between the local site read and central review. II. To determine if metabolic response on serial FDG-PET/CT from pre-therapy to 12 months of anti-PD-1 therapy, as determined centrally by various criteria, is associated with EFS. III. To determine if metabolic response on serial FDG-PET/CT from 12 to 24 months after start of anti-PD-1 therapy, as determined centrally by various criteria, is associated with EFS. BIOMARKER OBJECTIVE: I. To bank tumor samples and peripheral blood for future biomarker studies. OUTLINE: Patients continue their standard of care anti-PD-1 therapy and are then assigned to 1 of 2 arms. STANDARD OF CARE: Treatment may consist of the following regimens: 1) nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W) or every 4 weeks (Q4W); 2) pembrolizumab IV over 30 minutes every 3 weeks (Q3W) or every 6 weeks (Q6W); 3) nivolumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by nivolumab IV over 30 minutes Q2W or Q4W; or 4) pembrolizumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by pembrolizumab IV over 30 minutes Q3W or Q6W. Treatment continues until 52 weeks from start of standard of care anti-PD-1 therapy in the absence of disease progression or unacceptable toxicity. ARM A: Patients with a negative FDG-PET/CT scan or a positive FDG-PET/CT scan but with a negative biopsy for viable tumor discontinue the anti-PD-1 therapy and undergo active surveillance. ARM B: Patients with a positive FDG-PET/CT scan and positive biopsy for viable tumor or a positive FDG-PET/CT scan and biopsy not performed continue their standard of care anti-PD-1 therapy for 12 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up through week 97 and then every 3 months for up to 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 29, 2026
• Est. primary completion date: August 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• STEP 0 PRE-REGISTRATION INCLUSION CRITERIA
• Patient must have active advanced melanoma, defined as unresectable stage IIIB-IV by American Joint Committee on Cancer (AJCC) 8th edition
• Patient must have melanoma originating from cutaneous, acral-lentiginous, or mucosal primary sites. Patients with melanoma of unknown primary site are eligible. Patients must not have melanoma from an ocular primary site
• Patient must have had measurable disease by immune related Response Evaluation Criteria in Solid Tumors (imRECIST) prior to start of initial anti-PD-1 therapy
• Patient must be actively receiving standard of care anti-PD-1 therapy, currently be 52 weeks (+/- 2 weeks) from start of anti-PD-1 therapy, and have not experienced a toxicity that prevents them from continuing on therapy. Permitted systemic anti-PD-1

therapy regimens include:

• Nivolumab 240 mg IV every (Q)2weeks or 480 mg IV Q4weeks
• Pembrolizumab 200 mg IV Q3weeks or 400 mg IV Q6weeks
• Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg IV Q3weeks induction x 4 doses, followed by nivolumab 240 mg IV Q2weeks or 480 mg IV Q4weeks maintenance
• Nivolumab 3 mg/kg plus Ipilimumab 1 mg/kg IV Q3weeks induction x 4 doses, followed by nivolumab 240 mg IV Q2weeks or 480 mg IV Q4weeks maintenance
• Pembrolizumab 2 mg/kg (or 200 mg flat dose) plus Ipilimumab 1 mg/kg IV Q3weeks induction x 4 doses, followed by pembrolizumab 200 mg IV Q3weeks or 400 mg IV Q6weeks maintenance
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients with detectable viral loads are excluded as it is unclear if these patients have a low risk of melanoma progression off anti-PD-1 treatment
• 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
• 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
• 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 must have experienced complete response, partial response, or stable disease on restaging CT scans by imRECIST that is maintained on restaging scans obtained at week 52 (+/- 2 weeks) from start of initial anti-PD-1 therapy
• Patient must have completed an FDG-PET/CT scan at week 52 (+/- 2 weeks) from start of initial anti-PD-1 therapy
• Patients with PET/CT positive for hypermetabolic lesions: If a core needle, punch or excisional biopsy and pathological review of a representative lesion was not

performed prior to pre-registration (Step 0) must either:

• Be amenable to undergo a biopsy. Patient must not be on anticoagulation therapy or, if on anti-coagulation therapy, patient must be able to hold treatment for a biopsy procedure (core needle, punch or excisional biopsy). Anti-coagulation therapy is defined as low molecular weight heparin, warfarin, factor Xa inhibitor, or direct thrombin inhibitor
• Have documentation of inability to perform the biopsy due to feasibility or safety concerns
• Leukocytes >= 3,000/mcL (obtained =< 4 weeks prior to protocol registration)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 4 weeks prior to protocol registration)
• Platelets >= 100,000/mcL (obtained =< 4 weeks prior to protocol registration)
• Total bilirubin =< institutional upper limit of normal (ULN) (patients with history of Gilbert's syndrome are permitted to have a total bilirubin > 1.5 x institutional ULN) (obtained =< 4 weeks prior to protocol registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 4 weeks prior to protocol registration)
• Creatinine =< 1.5 x institutional ULN (obtained =< 4 weeks prior to protocol registration)
• STEP 1 REGISTRATION INCLUSION CRITERIA
• Patient met all eligibility criteria outlined above
• Patient must register to Step 1 within 4 weeks of registration to Step 0
• Patients must meet one of the following criteria:
• Patient had no positive hypermetabolic lesions on the week 52 FDG-PET/CT.
• Patients with positive hypermetabolic lesion(s) on the week 52 FDG-PET/CT (positive hypermetabolic = standard uptake volume [SUV] > pooled mediastinal

blood), one of the following must have occurred:

• A representative lesion was biopsied (core needle, punch or excisional biopsy) within 14 days of registration to Step 0 and subsequent pathology review performed to determine the presence or absence of viable tumor
• Documentation is present that the patient is not able to undergo biopsy of a hypermetabolic lesion due to feasibility or safety concerns, i.e., the lesion location that is not amenable to biopsy

Exclusion Criteria:

• STEP 0 PRE-REGISTRATION EXCLUSION CRITERIA
• Patient must not be receiving concurrent anti-tumor therapies in addition to the standard of care anti-PD-1 regimens. Patients who are receiving bisphosphonates and RANKL inhibitors for management of bone metastases are eligible
• Patient must not have brain metastases
• Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the anti-PD-1 regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration 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)
• Women of childbearing potential and sexually active males must not conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of study registration and continuing until at least 5 months after the last dose of anti-PD-1 treatment for female patients and for at least 7 months after the last dose of anti-PD-1 treatment for male patients who are sexually active with a women of childbearing potential (WOCBP)

Related Conditions & MeSH terms

• Advanced Melanoma
• Clinical Stage III Cutaneous Melanoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Melanoma
• Melanoma of Unknown Primary
• Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IIID Cutaneous Melanoma AJCC v8
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Skin Neoplasms
• Unresectable Acral Lentiginous Melanoma
• Unresectable Melanoma
• Unresectable Mucosal Melanoma

Intervention

Biological:
• Ipilimumab
Given IV
• Nivolumab
Given IV

Other:
• Patient Observation
Undergo active surveillance

Biological:
• Pembrolizumab
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center	Adrian	Michigan
United States	Riverwood Healthcare Center	Aitkin	Minnesota
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
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	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	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	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Essentia Health - Baxter Clinic	Baxter	Minnesota
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Boston Medical Center	Boston	Massachusetts
United States	Boulder Community Foothills Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
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	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
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	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
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	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
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	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	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Western Surgical Care	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	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Columbus Oncology and Hematology Associates	Dublin	Ohio
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Essentia Health - Ely Clinic	Ely	Minnesota
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Rocky Mountain Cancer Centers - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	The Melanoma and Skin Cancer Institute	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Saint Francis Hospital	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Glens Falls Hospital	Glens Falls	New York
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Essentia Health-Hayward Clinic	Hayward	Wisconsin
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Essentia Health - International Falls Clinic	International Falls	Minnesota
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	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	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	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	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	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Essentia Health - Moose Lake Clinic	Moose Lake	Minnesota
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Lakeland Hospital Niles	Niles	Michigan
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	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	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	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	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	Essentia Health Sandstone	Sandstone	Minnesota
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Community Medical Center	Scranton	Pennsylvania
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
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	North Grove Medical Park	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Spartanburg Medical Center - Mary Black Campus	Spartanburg	South Carolina
United States	Essentia Health-Spooner Clinic	Spooner	Wisconsin
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Essentia Health Saint Mary's Hospital - Superior	Superior	Wisconsin
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC-Upper Valley	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	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
Other	Determine FDG-PET/CT positivity between the local site read and central review	Determining agreement between local and central review of FDG-PET/CT positivity	Up to 5 years
Other	Metabolic response on serial FDG-PET/CT	Metabolic response by serial FDG-PET/CT scan from baseline to 12 month time-point (Arm A) will be associated with EFS (Arm A) and with EFS (Arm B).	Baseline to 12 months of anti-PD-1 therapy
Other	Metabolic response on serial FDG-PET/CT	Metabolic response by serial FDG-PET/CT scan from the 12 month to 24 month time points (Arm B) will be associated with EFS (Arm A) and with EFS (Arm B).	12 months to 24 months after start of anti-PD-1 therapy
Other	Banking samples for future biomarker studies	Will bank tumor samples and peripheral blood for future biomarker studies.	Up to 5 years
Primary	Event free survival (EFS) rate (Arm A)	Event is defined as recurrence, progression or melanoma-specific death. The distribution of EFS will be evaluated using the method of Kaplan-Meier.	At 12 months
Secondary	Rates of pathologic response (Arm B)	Will be defined as the absence of residual viable melanoma in the resected metastasis site as assessed on local pathology review. Pathologic response rate will be estimated in patients with tumor biopsies where positive hypermetabolic activity was present on FDG-PET/CT scan after 12 month of anti-PD-1 therapy on Arm B. 95% confidence intervals (CIs) will be provided for all estimated rates.	After 12 months of anti-PD-1 therapy
Secondary	EFS	The distribution of EFS will be evaluated using the method of Kaplan-Meier.	At 24 months
Secondary	Overall survival	Overall 24 month EFS for patients in Arm B will be summarized.	At 24 months
Secondary	Percentage of patients who remain on treatment beyond 12 months	Will determine the percentage of patients who remain on treatment beyond 12 months because of positive fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scan and positive biopsy for residual disease (or unable to obtain a biopsy).	Up to 5 years
Secondary	Incidence rates of treatment-related adverse events -12 months from start of treatment in patients who discontinue anti-PD-1 therapy at 12 months (Arm A) and in patients who continue anti-PD-1 therapy beyond 12 months (Arm B)	95% CIs will be provided for all estimated rates.	Up to 5 years