Duration of Anti-PD-1 Therapy in Metastatic Melanoma (STOP-GAP)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Unresectable/Metastatic Melanoma
• Intervention / Treatment: Drug: Intermittent PD-1 inhibitor therapy; Drug: Continuous PD-1 inhibitor therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 614
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Janet Dancey; Phone Number: 613-533-6430; Email: jdancey@ctg.queensu.ca

Study Locations

• Australia
  • Herston, Australia, 4029
    • Recruiting
    • Royal Brisbane and Womens Hospital
    • Contact: Melissa Eastgate
  • Mildura
    • VIC, Mildura, Australia, 3500
      • Recruiting
      • Mildura Base Public Hospital
      • Contact: Jose Leal
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Recruiting
      • Coffs Habour Health Campus - NCCI
      • Contact: Karen Briscoe
    • Wagga Wagga, New South Wales, Australia, 2650
      • Not yet recruiting
      • Riverina Cancer Care Centre Wagga Wagga
      • Contact: Renuka Chittajallu
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle Hospital
      • Contact: Ina Nordman
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Contact: Matteo Carlino
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • Sunshine Coast University Hospital
      • Contact: Mary Wagih Azer; Phone Number: 651 7 520-0200
    • Brisbane, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
      • Contact: Euan Walpole
    • Cairns, Queensland, Australia, 4870
      • Recruiting
      • Cairns Hospital
      • Contact: Megan Lyle
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital
      • Contact: Marcin Dzienis
  • South A.
    • Woodville, South A., Australia, 5011
      • Recruiting
      • The Queen Elizabeth Hospital
      • Contact: Rachel Roberts-thomson
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
      • Contact: Muhammad Alamgeer
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Hospital
      • Contact: Mark Shackleton
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
      • Contact: John Walker; Phone Number: 780 432-8340
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Recruiting
      • BCCA - Fraser Valley Cancer Centre
      • Contact: Christopher Lee; Phone Number: 604 930-4017
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BCCA - Vancouver Cancer Centre
      • Contact: Kerry J. Savage; Phone Number: 2641 604 877-6000
    • Victoria, British Columbia, Canada, V8R 6V5
      • Recruiting
      • BCCA - Vancouver Island Cancer Centre
      • Contact: Vanessa Bernstein; Phone Number: 250 519-5571
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 5N5
      • Recruiting
      • Horizon Health Network
      • Contact: M. Saleem Raza; Phone Number: 506 447-4095
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Recruiting
      • Royal Victoria Regional Health Centre
      • Contact: Jessica Singh; Phone Number: 43560 705 728-9090
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre at Hamilton Health Sciences
      • Contact: Elaine McWhirter; Phone Number: 64609 905 387-9495
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: Tara Baetz; Phone Number: 6654 613 549-6666
    • Kitchener, Ontario, Canada, N2G 1G3
      • Recruiting
      • Grand River Regional Cancer Centre
      • Contact: Gregory J. Knight; Phone Number: 5262 519 749-4370
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Regional Cancer Program
      • Contact: John Lenehan; Phone Number: 519 685-8640
    • Mississauga, Ontario, Canada, L5M 2N1
      • Recruiting
      • Trillium Health Partners - Credit Valley Hospital
      • Contact: Sudha Rajagopal; Phone Number: 5135 905 813-1100
    • Oshawa, Ontario, Canada, L1G 2B9
      • Recruiting
      • Lakeridge Health Oshawa
      • Contact: Rama Koneru; Phone Number: 905 576-8711
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Xinni Song; Phone Number: 70208 613 737-7700
    • Sudbury, Ontario, Canada, P3E 5J1
      • Recruiting
      • Health Sciences North
      • Contact: Eoghan Malone
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network
      • Contact: Marcus Butler; Phone Number: 5485 416 946-4501
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Odette Cancer Centre
      • Contact: Teresa M. Petrella; Phone Number: 416 480-4270
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • The Research Institute of the McGill University
      • Contact: Catalin Mihalcioiu; Phone Number: 514 934-1934
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Recruiting
      • Allan Blair Cancer Centre
      • Contact: Mussawar Iqbal; Phone Number: 306 766-2691
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Recruiting
      • Saskatoon Cancer Centre
      • Contact: Tahir Abbas; Phone Number: 306 655-2710

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Intermittent PD-1 Inhibitor therapy; Any PD-1 inhibitor that is commercially available, government approved and publicly funded. Dose as recommended by the manufacturer.	Drug: Intermittent PD-1 inhibitor therapy
Active Comparator: Arm 2: Continuous PD-1 Inhibitor therapy; Any PD-1 inhibitor that is commercially available, government approved and publicly funded. Dose as recommended by the manufacturer.	Drug: Continuous PD-1 inhibitor therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	7 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Melanoma and Skin Cancer Trials Limited
• Investigators: Study Chair: Xinni Song, Ottawa Hospital Research Institute; Study Chair: Tara Baetz, Cancer Centre of Southeastern Ontario at Kingston

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2016
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (Estimated): July 1, 2016

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: ME13; UQ-QMP-0001 (Other Identifier: QMP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No