PD-1 Inhibitor Therapy Duration for Melanoma
(STOP-GAP Trial)
Recruiting in Palo Alto (17 mi)
+38 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Canadian Cancer Trials Group
Must be taking: PD-1 inhibitors
Disqualifiers: Contraindications to PD-1, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 8 jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to compare the effects on patients with metastatic melanoma of taking a government approved and paid-for PD-1 inhibitor intermittently, with taking the same type of agent continuously. Researchers want to see if the two ways of giving this type of treatment work equally well in extending the life of patients with melanoma, or not.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you are on anti-PD-1 therapy, you may need to stop it if you are randomized to the intermittent treatment group.
What data supports the effectiveness of the PD-1 inhibitor drug for melanoma?
Research shows that PD-1 inhibitors can lead to long-lasting benefits for melanoma patients, with some achieving complete or partial responses even after stopping the drug. Studies indicate that these drugs have improved survival rates, with some patients experiencing durable remissions.
12345Is PD-1 inhibitor therapy generally safe for humans?
PD-1 inhibitors, like nivolumab and pembrolizumab, are generally safer than older treatments, but they can still cause side effects, mostly related to the immune system. Most side effects are mild and manageable, but some can be serious, affecting the skin, lungs, and nerves.
678910How is PD-1 inhibitor therapy different from other treatments for melanoma?
PD-1 inhibitors are unique because they help the immune system recognize and attack melanoma cells by blocking a protein that prevents immune cells from attacking cancer. Unlike traditional chemotherapy, which directly kills cancer cells, PD-1 inhibitors work by enhancing the body's natural immune response to fight the cancer.
14111213Eligibility Criteria
Adults with metastatic melanoma who are eligible for government-funded PD-1 inhibitor therapy can join. They must have stable disease, including brain metastases if present, and be willing to complete questionnaires in English or French. Those not willing to potentially pause treatment or with contraindications to PD-1 inhibitors cannot participate.Inclusion Criteria
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
My cancer cannot be removed by surgery and can be monitored but doesn't need to be measurable.
My cancer has not worsened and I have no new or growing brain tumors for at least 4 weeks.
+12 more
Exclusion Criteria
I am not willing to stop my anti-PD-1 therapy if required.
I cannot take PD-1 inhibitors due to health risks.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive PD-1 inhibitor therapy either continuously or intermittently for up to 2 years
Up to 104 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Participant Groups
The trial is testing two methods of administering a PD-1 inhibitor: intermittently stopping and restarting treatment versus continuous use without breaks. The goal is to see which method better extends the lives of patients with metastatic melanoma.
2Treatment groups
Active Control
Group I: Arm 1: Intermittent PD-1 Inhibitor therapyActive Control1 Intervention
Any PD-1 inhibitor that is commercially available, government approved and publicly funded. Dose as recommended by the manufacturer.
Group II: Arm 2: Continuous PD-1 Inhibitor therapyActive Control1 Intervention
Any PD-1 inhibitor that is commercially available, government approved and publicly funded. Dose as recommended by the manufacturer.
PD-1 inhibitor is already approved in United States, United States, United States, European Union, European Union, European Union, China, United States for the following indications:
🇺🇸 Approved in United States as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Kidney cancer
- Head and neck cancers
- Hodgkin lymphoma
- Colorectal cancer
- Hepatocellular carcinoma
- Urothelial carcinoma
🇺🇸 Approved in United States as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck cancers
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Endometrial carcinoma
- Cervical cancer
- Esophageal cancer
- Cutaneous squamous cell carcinoma
🇺🇸 Approved in United States as Cemiplimab (Libtayo) for:
- Cutaneous squamous cell carcinoma
- Non-small cell lung cancer
🇪🇺 Approved in European Union as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Kidney cancer
- Head and neck cancers
- Hodgkin lymphoma
- Colorectal cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck cancers
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
🇪🇺 Approved in European Union as Cemiplimab (Libtayo) for:
- Cutaneous squamous cell carcinoma
🇨🇳 Approved in China as Toripalimab (Loqtorzi) for:
- Melanoma
- Non-small cell lung cancer
- Urothelial carcinoma
🇺🇸 Approved in United States as Toripalimab (Loqtorzi) for:
- Nasopharyngeal carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
London Health Sciences Centre Research Inc.London, Canada
Saskatoon Cancer CentreSaskatoon, Canada
BCCA - SurreySurrey, Canada
BCCA - VancouverVancouver, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Canadian Cancer Trials GroupLead Sponsor
Melanoma and Skin Cancer Trials LimitedCollaborator
References
Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma. [2023]Randomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective.
Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma. [2022]Historically, the median overall survival for patients with stage IV melanoma was less than 1 year and the 5-year survival rate was ∼10%. Recent advances in therapy have raised 5-year survival expectations to ∼20%. Notably, a subset of melanoma patients who receive immunotherapy with high-dose interleukin-2, and now ipilimumab, can achieve long-term survival of at least 5 years. A major goal in melanoma research is to increase the number of patients who experience this overall survival benefit. In this review, we discuss the attributes of immunotherapy and newer targeted agents, and consider how combination strategies might improve the chances of achieving durable benefit and long-term survival. We also discuss three areas that we believe will be critical to making further advances in melanoma treatment. To better understand the clinical profile of patients who achieve long-term survival with immunotherapy, we first present data from ipilimumab clinical trials in which a subset of patients experienced durable responses. Second, we discuss the limitations of traditional metrics used to evaluate the benefits of immunotherapies. Third, we consider emerging issues that clinicians are currently facing when making treatment decisions regarding immunotherapy. A better understanding of these novel treatments may improve survival outcomes in melanoma, increase the number of patients who experience this overall survival benefit, and inform the future use of these agents in the treatment of other cancer types.
Melanoma and Immune Checkpoint Inhibitors. [2019]Prognosis of patients with advanced melanoma is dismal with a median overall survival of about 8 months and 5-year overall survival from a diagnosis of metastatic disease of roughly 10%. However, immune checkpoint inhibitors have brought indispensable benefits to melanoma patients. Here we will review the recent clinical efficacy and adverse events of immune checkpoint inhibitors for melanoma patients.
Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup. [2023]Immunotherapy has improved the survival of patients with stage IV melanoma. In responders, clinical benefits may be long-lasting and persist even after treatment discontinuation. The optimal duration of anti-PD1 (anti-Programmed cell death-1) therapy in metastatic melanoma patients remains to be elucidated. Moreover, limited data are available on clinical outcomes of patients that discontinued anti-PD1 immunotherapy in a real-life setting. The aim of this study was to evaluate the progression-free survival (PFS) in patients with metastatic melanoma who interrupted anti-PD-1 treatment in the in the absence of disease progression.
Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice. [2022]There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.
The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.
Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. [2021]Programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are promising cancer immunotherapy. Their dermatologic safety profiles are still poorly understood. The purpose of this article is to evaluate the incidence of selected dermatologic and mucosal adverse effects (AEs) and determine the risk of developing these adverse events associated with PD-1/PD-L1 inhibitors, compared with chemotherapy or ipilimumab.
A 65-Year-Old Male with Primary Central Nervous System Diffuse Large B-Cell Lymphoma on Nivolumab with Oral Mucositis and Targetoid Plaques. [2022]The development of programmed cell death-1 (PD-1) inhibitors has greatly improved patient outcomes in the treatment of a variety of advanced malignancies. These novel immunotherapies are not without adverse effects, the most common of which are dermatologic.
PD-1 Inhibitor Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events . [2018]Programmed cell death protein 1 (PD-1) inhibitor therapies are now a standard treatment for advanced melanoma and other tumor types. The immune-related adverse events (irAEs) associated with PD-1 inhibitor therapy are drastically different from the AEs associated with chemotherapy. Because these irAEs reflect immune system activation rather than side effects of therapy, nurses should be cognizant of the range of organ systems potentially affected as well as likely clinical presentations. .
Anti-PD1/PDL1 induced psoriasis. [2022]Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported.
Limited-duration anti-PD-1 therapy for patients with metastatic melanoma. [2020]Purpose: To date, no clinical study has reported on the optimal treatment duration of PD-1 blockade in patients with metastatic melanoma. Worldwide, concern has been expressed that due to the high cost of anti-PD-1 therapy, it is not available for all patients. After approval of anti-PD-1 therapy as a first-line treatment, the Helsinki University Hospital institutional board for new drugs decided to treat the first patient cohort within a limited treatment duration program in order to offer this treatment to as many patients as possible.Patients and methods: The first 40 patients with metastatic melanoma initiating treatment at Helsinki University Hospital were to be treated within a six months maximum limited duration program. Patient follow-up was systematic according to a prospectively planned treatment protocol to enable evaluation of treatment efficacy and the safety of this treatment approach.Results: Thirty-eight patients were treated within the program. Seventeen out of these 38 patients completed the six-month regimen. Five discontinued treatment early due to toxicity, and 16 discontinued due to progressive disease. The response rate (RR) for all patients was 39%, but only 33% of these responses are ongoing. Median progression-free survival (PFS) for patients who completed the six-month therapy was 12 months (range, two to 44 months), and median overall survival (OS) has not yet been reached.Conclusions: Although RR is comparable to published data, the response duration is shorter. Based on our results, limiting treatment to only six months may increase the risk of shortening response duration.
Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity. [2018]Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited.
Beyond the 5-year milestone: Long-term survivorship of melanoma patients treated off-trial with anti-PD-1. [2023]Little is known about the long-term outcomes of anti-PD-1 treated patients with melanoma beyond 5 years, especially for patients treated off clinical trials. This retrospective cohort study includes patients with unresectable stage III/IV nonuveal melanoma treated with anti-PD-1 off-trial at Memorial Sloan Kettering Cancer Center between 2014 and 2017 who survived at least 5 years following their first anti-PD-1 dose (N = 139). We characterized overall survival (OS), melanoma-specific survival (MSS) estimates, treatment-free survival rates, and subsequent treatment courses. Median follow-up among 5-plus year survivors (N = 125) was 78.4 months (range 60.0-96.3). OS at year 7 (2 years post 5-year landmark) was 90.1% (95% CI: 83.0%-94.3%). Fourteen deaths occurred, seven due to melanoma. MSS at year 7 (2 years post 5-year landmark) was 95.0% (95% CI: 33.5%-95.2%). In patients who completed anti-PD-1 based therapy and did not require subsequent treatment by 5 years (N = 80), the probability of not requiring additional treatment for an additional 2 years was 95.7% (95% CI: 91.0%-100%). Patients treated with anti-PD-1 regimens off clinical trials who survive at least 5 years from initial anti-PD-1 treatment can be reassured of their excellent long-term prognosis, particularly if they did not require additional melanoma treatment during the first 5 years.