Clinical trial NCT02821013: Duration of Anti-PD-1 Therapy in Metastatic Melanoma
Official title: A Randomized Phase III Trial of the Duration of Anti-PD-1 Therapy in Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Unresectable/Metastatic Melanoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Melanoma and Skin Cancer Trials Limited
First posted: 2016-07-01
Enrollment: 614
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: 7 years
Secondary outcomes:
measure: Progression-free survival using RECIST 1.1 / Immune-Related RECIST (irRECIST)
timeFrame: 7 years
measure: Response rate using RECIST 1.1 / Immune-Related RECIST (irRECIST)
timeFrame: 7 years
measure: Duration of response using RECIST 1.1 / Immune-Related RECIST (irRECIST)
timeFrame: 7 years
measure: Number and severity of adverse events using CTCAE v 4.0
timeFrame: 7 years
measure: Quality of Life measured by EORTC QLQ-C30
timeFrame: 7 years
measure: Economic evaluation consisting of both healthcare utilization and health utilities measured by the EQ-5D questionnaire
timeFrame: 7 years
Other outcomes:
Locations:
city: Victoria
country: Australia
facility: Mildura Base Public Hospital
state: Mildura
city: Coffs Harbour
country: Australia
facility: Coffs Habour Health Campus - NCCI
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre Wagga Wagga
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South A.
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Surrey
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver
state: British Columbia
city: Victoria
country: Canada
facility: BCCA - Victoria
state: British Columbia
city: Fredericton
country: Canada
facility: Horizon Health Network
state: New Brunswick
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Kitchener
country: Canada
facility: Waterloo Regional Health Network (WRHN)
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre Research Inc.
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: The Research Institute of the McGill University
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Xinni Song
role: STUDY_CHAIR
affiliation: Cancer Centre of Southeastern Ontario at Kingston
name: Tara Baetz
role: STUDY_CHAIR
References: