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Active Not RecruitingNCT04462406

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

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

Status
Active Not Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
150 (estimated)
Sponsor
ECOG-ACRIN Cancer Research Group · Network
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed 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.

Conditions

Interventions

TypeNameDescription
BIOLOGICALIpilimumabGiven IV
BIOLOGICALNivolumabGiven IV
OTHERPatient ObservationUndergo active surveillance
BIOLOGICALPembrolizumabGiven IV

Timeline

Start date
2021-02-09
Primary completion
2026-08-29
Completion
2026-08-29
First posted
2020-07-08
Last updated
2026-03-23

Locations

482 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04462406. Inclusion in this directory is not an endorsement.