Overview

This trial is active, not recruiting.

Condition stage iii skin melanoma
Treatments surgery of the tumor, infusion with ipilimumab 3 mg/kg q3wks, infusion with nivolumab 1 mg/kg q3wks
Phase phase 1
Sponsor The Netherlands Cancer Institute
Collaborator Bristol-Myers Squibb
Start date April 2015
End date April 2017
Trial size 20 participants
Trial identifier NCT02437279, CA209-278, N14OPC, NL51280.031.14

Summary

This is a two-arm Phase 1b feasibility trial consisting of 20 patients receiving the combination of ipilimumab+nivolumab, either adjuvant, or split neo-adjuvant and adjuvant.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Post-surgery infusion for 12 weeks with the combination of ipilimumab+nivolumab
surgery of the tumor
infusion with ipilimumab 3 mg/kg q3wks
infusion with nivolumab 1 mg/kg q3wks
(Active Comparator)
A split design 6 weeks upfront surgery and 6 weeks post-surgery infusion with the combination of ipilimumab+nivolumab
surgery of the tumor
infusion with ipilimumab 3 mg/kg q3wks
infusion with nivolumab 1 mg/kg q3wks

Primary Outcomes

Measure
The alteration in magnitude of the neo-antigen specific T cell response in the time interval pre- to post-adjuvant therapy in peripheral blood
time frame: 12 weeks from baseline
Safety as measured by SUSARs.
time frame: 12 weeks from baseline
The alteration in breadth of the neo-antigen specific T cell response in the time interval pre- to post-adjuvant therapy in peripheral blood
time frame: 12 weeks from baseline
Feasibility as measured adherence to the timelines in the study protocol.
time frame: 12 weeks from baseline

Secondary Outcomes

Measure
Recurrence Free Survival, as determined according to RECIST 1.1 criteria.
time frame: Until progression, median 10 months.
Rate of adverse events and late adverse events
time frame: Until end of follow-up, median 3 years.
Type of adverse events and late adverse events
time frame: Until end of follow-up, median 3 years.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adults at least 18 years of age - World Health Organization (WHO) Performance Status 0 or 1 - Histologically confirmed stage IIIB metastatic cutaneous melanoma, palpable disease (non-transit only) of the axilla or groin - Patient willing to undergo triple tumor biopsies during screening and in case of disease progression - No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 - No immunosuppressive medications within 6 months prior study inclusion - Presence of at least two of the defined HLA alleles (Table 1, see appendix) - Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN - normal LDH - Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug - Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of ipilimumab+nivolumab - Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product - Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception Exclusion Criteria: - Distantly metastasized melanoma - Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy - Prior CTLA-4 or PD-1/PD-L1 targeting immunotherapy - Radiotherapy prior or post surgery within this trial - Patients will be excluded if they are positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection - Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) - Allergies and Adverse Drug Reaction - History of allergy to study drug components - History of severe hypersensitivity reaction to any monoclonal antibody - Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events; - Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids; - Use of other investigational drugs before study drug administration 30 days and 5 half-times before study inclusion - Pregnant or nursing.

Additional Information

Official title Feasibility Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab in Stage III Melanoma Patients
Principal investigator Christian Blank, MD PhD
Description Patients with stage III melanoma with palpable disease, naïve for CTLA-4/PD-1/PD-L1 immunotherapy, will be treated either post-surgery for 12 weeks with the combination of ipilimumab+nivolumab or in a split design for 6 weeks upfront surgery and for 6 weeks postsurgery. It is a two-arm Phase 1b feasibility trial consisting of 20 patients, 10 in each arm. At different timepoints tumor biopsies and blood for PBMCs will be taken for translational research. Also scans will be done on specific timepoints. The study will be held to determine safety, feasibility, and the immune-activating capacity of short-term combined neo-adjuvant and adjuvant ipilimumab + nivolumab. And to determine relapse free survival (RFS), any late adverse events, pharmacokinetics/pharmacodynamics, and the correlation between RFS and changes in neo-antigen specific T cell response.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by The Netherlands Cancer Institute.