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NCT04462406

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

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-09

Study Completion Date

2026-08-29

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Melanoma Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 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 Unresectable Acral Lentiginous Melanoma Unresectable Melanoma Unresectable Mucosal Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

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)
* 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

* 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)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey T Gibney

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

EA6192

Identifier Type: OTHER

Identifier Source: secondary_id

EA6192

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

EA6192

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

Arm A (active surveillance)

Patient Observation

Arm B (nivolumab, pembrolizumab, ipilimumab)

Nivolumab

Pembrolizumab

Standard of Care (nivolumab, pembrolizumab, ipilimumab)

Ipilimumab

Nivolumab

Pembrolizumab

Interventions

Ipilimumab

Nivolumab

Patient Observation

Pembrolizumab

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Responsible Party

Principal Investigators

Geoffrey T Gibney

Locations

Thomas Hospital

Mobile Infirmary Medical Center

Fairbanks Memorial Hospital

Cancer Center at Saint Joseph's

Banner University Medical Center - Tucson

University of Arizona Cancer Center-North Campus

Mercy Hospital Fort Smith

CHI Saint Vincent Cancer Center Hot Springs

CARTI Cancer Center

University of Arkansas for Medical Sciences

Kaiser Permanente-Deer Valley Medical Center

Mission Hope Medical Oncology - Arroyo Grande

Mercy Cancer Center - Carmichael

Mercy San Juan Medical Center

Kaiser Permanente Dublin

Mercy Cancer Center - Elk Grove

Kaiser Permanente-Fremont

Fresno Cancer Center

Kaiser Permanente-Fresno

The Angeles Clinic and Research Institute - West Los Angeles Office

Cedars Sinai Medical Center

Mercy Cancer Center

Kaiser Permanente-Modesto

Kaiser Permanente Oakland-Broadway

Kaiser Permanente-Oakland

Kaiser Permanente-Rancho Cordova Cancer Center

Kaiser Permanente- Marshall Medical Offices

Kaiser Permanente-Richmond

Mercy Cancer Center - Rocklin

Rohnert Park Cancer Center

Kaiser Permanente-Roseville

The Permanente Medical Group-Roseville Radiation Oncology

Kaiser Permanente Downtown Commons

Mercy Cancer Center - Sacramento

Kaiser Permanente-South Sacramento

South Sacramento Cancer Center

Kaiser Permanente-San Francisco

Kaiser Permanente-Santa Teresa-San Jose

Kaiser Permanente San Leandro

Pacific Central Coast Health Center-San Luis Obispo

Kaiser San Rafael-Gallinas

Kaiser Permanente Medical Center - Santa Clara

Mission Hope Medical Oncology - Santa Maria

Kaiser Permanente-Santa Rosa

Kaiser Permanente Cancer Treatment Center

Kaiser Permanente-South San Francisco

Kaiser Permanente-Stockton