What side effects are associated with this type of intervention?

The most common treatments for melanoma, particularly anti-PD-1 therapies like nivolumab and pembrolizumab, are associated with a range of side effects. These can include immune-related adverse events such as skin reactions (rash, pruritus), endocrine disorders (thyroid dysfunction, adrenal insufficiency), gastrointestinal issues (diarrhea, colitis), and pneumonitis. Other potential side effects include fatigue, musculoskeletal pain, and liver enzyme abnormalities. Severe adverse events, though less common, can lead to treatment discontinuation and may require immunosuppressive therapy.

What prior FDA approvals exist?

The FDA has approved several anti-PD-1 therapies for the treatment of melanoma, including pembrolizumab and nivolumab. These drugs are used to treat advanced or unresectable melanoma by blocking the programmed cell death protein 1 (PD-1) pathway, thereby enhancing the immune system's ability to fight cancer. Additionally, combination therapies such as nivolumab with ipilimumab have also received FDA approval for melanoma treatment. These therapies are similar to those being studied in the trial investigating biomarker-guided early discontinuation of anti-PD-1 therapy using PET/CT imaging and tumor biopsy.

What other types of research exist?

Promising novel alternatives for melanoma patients considering treatment in 2024 include: 1) Combination therapies involving anti-PD-1 agents with other immune checkpoint inhibitors like anti-CTLA-4 (e.g., nivolumab and ipilimumab), 2) Chimeric Antigen Receptor (CAR)-T cell therapies, 3) Personalized cancer vaccines, and 4) Novel immune-modulating agents targeting different pathways in the cancer-immunity cycle. Patients should discuss these options with their oncologist to determine the most appropriate treatment strategy based on their specific condition and the latest clinical trial availability.

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PD-1 Inhibitor

Biomarker-Guided Immunotherapy Discontinuation for Melanoma

Phase 2

Recruiting

Led By Geoffrey T Gibney

Research Sponsored by ECOG-ACRIN Cancer Research Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must have active advanced melanoma, defined as unresectable stage IIIB-IV by American Joint Committee on Cancer (AJCC) 8th edition

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

Must not have

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)

Patient must not have brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial uses drugs that boost the immune system to fight advanced melanoma that can't be surgically removed. It aims to see if doctors can safely shorten the treatment period by using imaging tests to guide decisions. Pembrolizumab and ipilimumab are immunotherapy drugs used to treat advanced melanoma, with pembrolizumab approved for younger patients and ipilimumab showing positive results in previous studies.

Who is the study for?

This trial is for adults with unresectable stage IIIB-IV melanoma. Participants must have had a positive response to initial anti-PD-1 therapy, meet specific health criteria (like normal organ function tests), and not be pregnant or breastfeeding. They should not have brain metastases or other conditions that could affect the study's safety or results.

What is being tested?

The PET-Stop Trial is testing if biomarkers from PET/CT imaging can guide when to safely stop immunotherapy in patients with advanced melanoma. It involves drugs like Pembrolizumab, Ipilimumab, Nivolumab, and patient observation to determine the effectiveness of early discontinuation.

What are the potential side effects?

Possible side effects include immune-related reactions such as inflammation in various organs, skin rash, fatigue, digestive issues like diarrhea or colitis, hormonal gland problems (like thyroid dysfunction), and potential infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My melanoma is advanced and cannot be removed by surgery.

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My cancer has not worsened after starting anti-PD-1 therapy according to recent scans.

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My melanoma comes from the skin, acral-lentiginous areas, or mucosal areas, not the eye.

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My cancer was measurable by specific criteria before starting anti-PD-1 therapy.

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I am able to get out of my bed or chair and move around.

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My hepatitis B virus load is undetectable with treatment.

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I am HIV positive, on treatment, and my viral load has been undetectable for the last 6 months.

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am using or willing to use effective birth control during and after the study as required.

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I do not have cancer that has spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event free survival (EFS) rate (Arm A)

Secondary study objectives

EFS

Therapeutic procedure

Overall survival

+2 more

Other study objectives

Tumor Markers

Determine FDG-PET/CT positivity between the local site read and central review

Metabolic response on serial FDG-PET/CT

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Standard of Care (nivolumab, pembrolizumab, ipilimumab)Experimental Treatment3 Interventions

Patients continue their standard of care anti-PD-1 therapy. Treatment may consist of the following regimens: 1) nivolumab IV over 30 minutes Q2W or Q4W; 2) pembrolizumab IV over 30 minutes Q3W or 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.

Group II: Arm A (active surveillance)Experimental Treatment1 Intervention

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.

Group III: Arm B (nivolumab, pembrolizumab, ipilimumab)Active Control2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Ipilimumab

2015

Completed Phase 3

~3070

Nivolumab

2015

Completed Phase 3

~4010

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for melanoma, particularly advanced stages, include immune checkpoint inhibitors such as anti-PD-1 therapies (e.g., pembrolizumab, nivolumab). These therapies work by blocking the programmed cell death protein 1 (PD-1) pathway, which tumors exploit to evade the immune system. By inhibiting PD-1, these drugs enhance the body's immune response against melanoma cells. This mechanism is crucial for melanoma patients as it can lead to durable responses and improved survival rates. The trial on biomarker-guided early discontinuation of anti-PD-1 therapy aims to optimize treatment duration, potentially reducing side effects and healthcare costs while maintaining efficacy.