Duration of Anti-PD-1 Therapy in Metastatic Melanoma

Unresectable/Metastatic Melanoma Clinical Trial

— STOP-GAP  

Official title:

A Randomized Phase III Trial of the Duration of Anti-PD-1 Therapy in Metastatic Melanoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02821013
• Other study ID #: ME13
• Secondary ID: UQ-QMP-0001
• Status: Recruiting
• Phase: Phase 3
• Start date: October 31, 2016
• Est. completion date: December 31, 2029

Study information

• Verified date: June 2024
• Source: Canadian Cancer Trials Group
• Contact: Janet Dancey
• Phone: 613-533-6430
• Email: jdancey[@]ctg.queensu.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The standard or usual treatment for this disease is to receive treatment with a class of agents known as PD-1 inhibitors, or also with the names anti-PD-1 therapy, immunotherapy and checkpoint inhibitors. PD-1 inhibitors turn on the immune system, so that it can fight the cancer cells in the body. Clinical trials have shown that PD-1 inhibitors (such as pembrolizumab and nivolumab) can shrink tumours and extend the life of patients with melanoma.

To-date, PD-1 inhibitors have been given to patients with melanoma continuously (non-stop), for as long as they remain beneficial, for up to a total duration of 2 years. The 2 year duration was chosen because doctors thought it was reasonable, and has been adopted as the standard or usual duration because it was shown to work in clinical trials. However, some recent observations suggest that PD-1 inhibitors may work just as well if they are given for a shorter time and/or in an intermittent schedule. Intermittent means to take breaks from receiving the drug when, and for as long as, the melanoma is better.

The investigators doing this study are interested to find out whether patients with melanoma live as long when the PD-1 inhibitors are given continuously (non-stop) or in an intermittent schedule (taking breaks). If the two ways of giving the treatment were to be shown to be just as good, benefits of an intermittent schedule may include less clinic visits and side effects, better quality of life, and less cost over time for the Health Care System. However, this is not known at present.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 614
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Minimum age 18 or as specified in the Product Monograph and eligible for public funding.

Inclusion Criteria:

• Histologically confirmed melanoma that is unresectable / metastatic (stage III or stage IV).

• Eligible to receive treatment with a government approved and publically-funded PD-1 inhibitor, according to the guidance / indications described in the Product Monograph / Provincial Formulary.

• Patients must have evidence of unresectable / metastatic disease, that is considered evaluable by the investigator and can be followed, but measurable disease is not mandatory.

• Patients with brain metastases are allowed, provided they are stable according to the following definitions:

1. Without evidence of progression for at least four weeks prior to randomization and have no evidence of new or enlarging brain metastases.

2. Treated with surgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases.

3. Treated with stereotactic radiosurgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases.

• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to randomization. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.

• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.

• Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

• Patients must be randomized prior to the start of, or within 16 weeks from, the initiation of PD-1 inhibitor treatment. For patients who are being randomized before the start of treatment, the PD-1 inhibitor should be started within 5 working days after randomization. Patients who initiate treatment with combination anti-PD-1 and anti-CTLA-4 therapies who experience toxicity may be randomized at the time prior to starting single-agent PD-1 inhibitor. Repeat imaging must be done within 50 days prior to randomization to ensure the patient has no evidence of disease progression

Exclusion Criteria:

• Patients not willing to stop anti-PD-1 therapy, if randomized to the intermittent arm.

• Patients with any contraindications to PD-1 inhibitors, as described in the Product Monograph or Provincial Formulary, and/or not eligible to receive anti-PD-1 therapy.

Related Conditions & MeSH terms

• Melanoma
• Unresectable/Metastatic Melanoma

Intervention

Drug:
• Intermittent PD-1 inhibitor therapy

• Continuous PD-1 inhibitor therapy

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Cairns Hospital	Cairns	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Coffs Habour Health Campus - NCCI	Coffs Harbour	New South Wales
Australia	Royal Brisbane and Womens Hospital	Herston
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Mildura Base Public Hospital	Victoria	Mildura
Australia	Riverina Cancer Care Centre Wagga Wagga	Wagga Wagga	New South Wales
Australia	Calvary Mater Newcastle Hospital	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville	South A.
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Horizon Health Network	Fredericton	New Brunswick
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Trillium Health Partners - Credit Valley Hospital	Mississauga	Ontario
Canada	The Research Institute of the McGill University	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Health Sciences North	Sudbury	Ontario
Canada	BCCA - Surrey	Surrey	British Columbia
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	BCCA - Vancouver	Vancouver	British Columbia
Canada	BCCA - Victoria	Victoria	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Melanoma and Skin Cancer Trials Limited

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		7 years
Secondary	Progression-free survival using RECIST 1.1 / Immune-Related RECIST (irRECIST)		7 years
Secondary	Response rate using RECIST 1.1 / Immune-Related RECIST (irRECIST)		7 years
Secondary	Duration of response using RECIST 1.1 / Immune-Related RECIST (irRECIST)		7 years
Secondary	Number and severity of adverse events using CTCAE v 4.0		7 years
Secondary	Quality of Life measured by EORTC QLQ-C30		7 years
Secondary	Economic evaluation consisting of both healthcare utilization and health utilities measured by the EQ-5D questionnaire		7 years