Melanoma Disease Site

Complexity Level: 2

Eligibility: MAIN INCLUSION CRITERA: Adults over 18 years of age with histological diagnosis of cutaneous melanoma or melanoma of unknown primary; Confirmed stage IV or advanced unresectable melanoma; Must have measurable disease; ECOG 0-2; No prior ICB treatment for advanced unresectable or metastatic disease; Able to ingest capsules. MAIN EXCLUSION CRITERIA: Antibiotic treatment in last 14 days; Corticosteroid use of > 10mg per day; Any absolute contraindications to FMT ; Active infections requiring antibiotic treatment.

Objectives: PRIMARY: Progression Free Survival (PFS) (per RECIST 1.1 and iRECIST) in standard of care ICB arm vs. standard of care ICB + FMT arm. SECONDARY: Compare treatment arms with respect to Overall Survival (OS), Objective Response Rate (ORR), and safety and tolerability. EXPLORATORY: To evaluate acquired donor-host similarity and its association with PFS in the FMT treatment arm; to evaluate engraftment and its association with progression-free survival in the FMT treatment arm; to evaluate the impact of FMT on the gut microbiota, gut metabolome and systemic immune response.

NCT Registration ID (from clinicaltrials.gov): NCT06623461
Participation: Open to member centres
NCI US Affiliation: No
Clinical Trials Application (Canada): Yes
Coordination: CCTG Led Trial
Status: Planned

Chair: (Canada) Dr. Arielle Elkrief, CHUM-Centre Hospitalier de l'Universite de Montreal, (514) 890-8000, (Canada) Dr. John Lenehan, London Regional Cancer Program, (519) 685-8640, (Canada) Dr. Bertrand Routy, CHUM-Centre Hospitalier de l'Universite de Montreal, (514) 890-8000, (Canada) Dr. Rahima Jamal, CHUM-Centre Hospitalier de l'Universite de Montreal, (514) 890-8444

Complexity Level: 2

Eligibility: Histologically proven mucosal melanoma by local pathology; central PD-L1 tissue tumour submission; Resected R0 or R1 disease; non-resected R2 or metastatic disease that is assessable and measurable; no prior systemic checkpoint inhibitor therapy of mucosal melanoma; age 18 or older.

Objectives: To compare the efficacy of adjuvant nivolumab (480mg q4 weeks) versus nivolumab plus cabozantinib (40 mg daily) in patients with mucosal melanoma. The primary objective will be measured as a comparison of duration of recurrence free survival (RFS) between the arms. Secondary objectives: OS, adverse effects by treatment arm, correlation between PD-L1 expresssion in tumour cells with RFS and OS; to evaluate ORR, DOR, PFS and OS of nivo plus cabo in patients who cannot undergo gross total resection of disease or have metastatic disease at baseline.

NCT Registration ID (from clinicaltrials.gov): NCT05111574
Participation: Open to member centres
NCI US Affiliation: Yes
Clinical Trials Application (Canada): Yes
Coordination: Intergroup Led Trial
Status: Open to Accrual
Activation Date: July 08, 2022

Chair: (Canada) Dr. Marcus Butler, University Health Network, (416) 946-4501 Ext. 5485

Complexity Level: 2

Eligibility: Patients are eligible if all the following requirements are met: 18 years or older, Histologically confirmed, primary invasive cutaneous melanoma: AJCC 8th edition Stage IIA-IIC (pT2b-pT4b), ECOG performance status 0-1 at randomisation, able to give informed consent, and comply with protocol treatment and follow up, randomisation and treatment must be performed within 120 days of diagnosis, patients must have no previous malignancy or primary except low-risk non-melanoma skin cancer (unless in remission and >5 years since diagnosis).

Objectives: This study will determine whether there is a difference in disease free survival for patients treated with either a 1cm excision margin or 2cm margin for clinical stage II (pT2b-pT4b) primary cutaneous melanoma (AJCC 8th edition).The study is designed to be able to prove or disprove that there is no difference in risk of melanoma recurrence between the two groups of patients. This study is designed to show that the risk of long-term pain associated with surgery can be reduced. If the study achieves its primary objective and demonstrates safety with a narrower margin, then we will also be able to determine how much of an impact the narrower excision has on patients in terms of improved quality of life and reduced side effects from the surgery and melanoma disease. This trial will also evaluate and determine the economic impact of narrower excision margins on the health services and society in general.

NCT Registration ID (from clinicaltrials.gov): NCT03860883
Participation: Open to member centres
NCI US Affiliation: No
Clinical Trials Application (Canada): No
Coordination: Intergroup Led Trial
Status: Open to Accrual
Activation Date: July 30, 2020

Chair: (Canada) Dr. Frances C. Wright, Odette Cancer Centre, (416) 480-5000 Ext. 3835

Complexity Level: 2

Eligibility: Participants of the main ME.13 trial enrolled at a Canadian centre who consent to submit a blood sample for buffy-coat and at least one additional biospecimen category.

Objectives: PRIMARY OBJECTIVE: To profile human bodily material (HBM) before, during and/or post-treatment with immune-checkpoint inhibitors (ICI) to characterize predictive biomarkers of key clinical outcomes of response, progression free and overall survival, and immune related toxicity during continuous and discontinuous ICI therapy regimens from the ME13 clinical trial. SECONDARY OBJECTIVES: (1) To identify spatial relationships between immune and melanoma cells in the pre-treatment tumour microenvironment (TME) that predict clinical outcomes; (2) To define mRNA expression and epigenetic changes in single exhausted CD8+ T cells and other immune cells that correlate with ICI response during continuous vs. intermittent ICI treatment; (3) To determine whether multi-dimensional molecular profiling of melanomas and circulating immune cells can identify a subset of markers to best predict clinical outcomes.

Participation: Open to member centres
NCI US Affiliation: No
Clinical Trials Application (Canada): No
Coordination: CCTG Led Trial
Status: Open to Accrual
Activation Date: November 14, 2023

Chair: (Canada) Dr. Ian Watson, Canada Research Chair II in Functional Genomics of M, (514) 398-3399

Complexity Level: 2

Eligibility: Patients with unresectable / metastatic (stage III or stage IV) melanoma, who are eligible to receive Health Canada approved, publically-funded PD-1 inhibitors.

Objectives: PRIMARY: To determine whether the Overall Survival (OS) of patients randomized to intermittent PD-1 inhibitor therapy is non-inferior to that of patients randomized to continuous PD-1 inhibitor therapy, in unresectable / metastatic (stage III or stage IV) melanoma. SECONDARY OBJECTIVES: (1) Progression-Free Survival, (2) Response rate and duration of response, (3) Adverse Events profile, (4) Quality of Life and (5) Economic Evaluation

NCT Registration ID (from clinicaltrials.gov): NCT02821013
Participation: Open to member centres
NCI US Affiliation: No
Clinical Trials Application (Canada): No
Coordination: CCTG Led Trial
Status: Open to Accrual
Activation Date: July 04, 2016

Chair: (Canada) Dr. Ian Watson, Canada Research Chair II in Functional Genomics of M, (514) 398-3399, (Canada) Dr. Xinni Song, Ottawa Hospital Research Institute, (613) 737-7700 Ext. 70208

Complexity Level: 2

Eligibility: Patients enrolled in this study must have completely resected melanoma of cutaneous origin (stage IIIA (N2a), IIIB, IIIC, or Stage IV) or of unknown primary. Patients with melanoma of mucosal or other non-cutaneous origin are eligible except for those with melanoma of ocular origin. Patients with a history of brain metastases are ineligible. For all patients, all disease must have been resected with negative pathological margins and no clinical radiologic or pathological evidence of any incompletely resected melanoma. Patients must be registered with 98 day of the last surgery performed to render the patient free of disease. Accrual rate is expected to be 45 patients per month with a total of 1240 patients enrolled in less than 2.5 years.

Objectives: Primary Objectives: a.Compare overall survival (OS) of patients with resected Stage III and IV melanoma treated with high dose interferon alfa-2b versus MK-3475 (pembrolizumab) b.Among patients who are PD-L1 positive, to compare OS of patients with resected Stage III and IV melanoma treated with high dose interferon alfa-2b versus MK-3475 (pembrolizumab) c.Compare relapse-free survival (RFS) of patients with resected Stage III and IV melanoma treated with high dose interferon alfa-2b to MK-3475 (pembrolizumab) d.Among patients who are PD-L1 positive, to compare RFS of patients with resected Stage III and IV melanoma treated with high dose interferon alfa-2b to MK-3475 (pembrolizumab) Secondary Objectives: a. Estimate OS and RFS for patients who are PD-L1 negative or PD-L1 indeterminate in this population. b. Compare OS and RFS of patients between the two regimens within PD-L1 positive and negative subgroups and to look at the interaction between PD-L1 and treatment arm.

NCT Registration ID (from clinicaltrials.gov): NCT02506153
Participation: Open to member centres
NCI US Affiliation: Yes
Clinical Trials Application (Canada): Yes
Coordination: Intergroup Led Trial
Status: Closed to Accrual
Activation Date: January 15, 2016 Closing Date: November 02, 2017

Chair: (Canada) Dr. Teresa M. Petrella, Odette Cancer Centre, (416) 480-4270

Complexity Level: 2

Eligibility: Patients enrolled in this study must have a diagnosis of primary cutaneous melanoma (high risk stage IIIB - IV as per AJCC Melanoma Staging System), and must have completely surgically resected disease at baseline. Patients must have been surgically rendered free of disease with negative margins, and must have a disease free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization. Some patients with disease recurrence after adequate surgical excision of the original primary melanoma are allowed as well, as specified in the protocol. A total of 1500 patients will be enrolled over 3.3 years. Accrual rate is expected to be 38 per month, and with additional follow up time, a total duration of study is expected to be less than 6 years.

Objectives: Primary Objectives: " To evaluate recurrence-free survival (RFS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (high dose ipilimumab; HIP) or 3 mg/kg (low dose ipilimumab: LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant). " To evaluate overall survival (OS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (HIP) or 3 mg/kg (LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant). Secondary Objectives: " To evaluate safety and tolerability of post-operative adjuvant ipilimumab therapy given at either 10 mg/kg (HIP) or 3 mg/kg (LIP).

NCT Registration ID (from clinicaltrials.gov): NCT01274338
Participation: Open to member centres
NCI US Affiliation: Yes
Clinical Trials Application (Canada): Yes
Coordination: Intergroup Led Trial
Status: Closed to Accrual
Activation Date: October 02, 2012 Closing Date: August 15, 2014

Chair: (Canada) Dr. Teresa M. Petrella, Odette Cancer Centre, (416) 480-4270

Complexity Level: 2

Eligibility: Patients with resected melanoma in the following categories: (1) T3-N0 (1.5-4 mm), (2) T4-N0 (> 4 mm), (3) T1-4 (microscopic, one lymph node positive).

Objectives: To compare the effect of treatment with four weeks of high dose IFN alpha-2b versus observation on relapse free survival and overall survival. Also, toxicities and quality-adjusted survival will be compared in the two groups.

NCT Registration ID (from clinicaltrials.gov): NCT00003641
Participation: Open to member centres
NCI US Affiliation: Yes
Clinical Trials Application (Canada): No
Coordination: Intergroup Led Trial
Status: Closed to Accrual
Activation Date: September 14, 1999 Closing Date: October 26, 2010

Chair: (Canada) Dr. Michael Smylie, Cross Cancer Institute, (780) 432-8757