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

Sponsor

Canadian Cancer Trials Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT02821013

Collaborator

Melanoma and Skin Cancer Trials Limited (Other)

614

Enrollment

Locations

Arms

161.9

Anticipated Duration (Months)

20.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable/Metastatic Melanoma	Drug: Intermittent PD-1 inhibitor therapy Drug: Continuous PD-1 inhibitor therapy	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

614 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 4, 2016

Anticipated Primary Completion Date :

Dec 31, 2027

Anticipated Study Completion Date :

Dec 31, 2029

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival [7 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coffs Habour Health Campus - NCCI	Coffs Harbour	New South Wales	Australia	2450
2	Riverina Cancer Care Centre Wagga Wagga	Wagga Wagga	New South Wales	Australia	2650
3	Calvary Mater Newcastle Hospital	Waratah	New South Wales	Australia	2298
4	Westmead Hospital	Westmead	New South Wales	Australia	2145
5	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
6	Cairns Hospital	Cairns	Queensland	Australia	4870
7	Gold Coast University Hospital	Southport	Queensland	Australia	4215
8	The Queen Elizabeth Hospital	Woodville	South A.	Australia	5011
9	Box Hill Hospital	Box Hill	Victoria	Australia	3128
10	Monash Medical Centre	Clayton	Victoria	Australia	3168
11	Alfred Hospital	Melbourne	Victoria	Australia	3004
12	Royal Brisbane and Womens Hospital	Herston		Australia	4029
13	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
14	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
15	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
16	Horizon Health Network	Fredericton	New Brunswick	Canada	E3B 5N5
17	Royal Victoria Regional Health Centre	Barrie	Ontario	Canada	L4M 6M2
18	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
19	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
20	Grand River Regional Cancer Centre	Kitchener	Ontario	Canada	N2G 1G3
21	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
22	Trillium Health Partners - Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
23	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
24	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
25	Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
26	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
27	University Health Network	Toronto	Ontario	Canada	M5G 2M9
28	The Research Institute of the McGill University	Montreal	Quebec	Canada	H4A 3J1
29	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
30	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

Canadian Cancer Trials Group
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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Canadian Cancer Trials Group

ClinicalTrials.gov Identifier:

NCT02821013

Other Study ID Numbers:

ME13
UQ-QMP-0001

First Posted:

Jul 1, 2016

Last Update Posted:

Jan 6, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Melanoma

Immune Checkpoint Inhibitors

Study Results

No Results Posted as of Jan 6, 2022