Clinical Trials Logo

Clinical Trial Summary

This randomized phase III trial studies how well pembrolizumab works compared with the current standard of care, physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab, in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether pembrolizumab is more effective than the current standard of care in treating patients with melanoma.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To compare overall survival (OS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon recombinant interferon alfa-2b (alfa-2b) or ipilimumab versus MK-3475 (pembrolizumab). II. Among patients who are PD-L1 positive, to compare OS of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab versus MK-3475 (pembrolizumab). III. To compare relapse-free survival (RFS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab to MK-3475 (pembrolizumab). SECONDARY OBJECTIVES: I. To estimate OS and RFS for patients who are PD-L1 negative or PD-L1 indeterminate in this population. II. To compare OS and RFS of patients between the two arms within PD-L1 positive and negative subgroups and to look at the interaction between PD-L1 (positive versus negative) and treatment arm. III. To assess the safety and tolerability of the regimens. ADDITIONAL OBJECTIVES: I. To bank tissue and whole blood in anticipation of future correlative studies in this patient population. II. To evaluate PD-L1 expression through immunohistochemistry assay. III. To evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of quality of life (QOL) using the Functional Assessment of Cancer Therapy (FACT)-Biological Response Modifiers (BRM), European Quality of Life Five Dimension Three Level Scale (EQ-5D-3L), and Functional Assessment of Chronic Illness Therapy Diarrhea (FACIT-D) between patients treated with physician/patient choice of either high-dose interferon alfa-2b or ipilimumab and MK-3475 (pembrolizumab). IV. Pharmacokinetic (PK) and anti-drug antibody (ADA) testing will be performed on all patients receiving MK-3475 (pembrolizumab). TRANSLATIONAL OBJECTIVES RELATED TO T-CELL RECEPTOR BETA CHAIN SEQUENCING: I. To evaluate the association between TCR beta variable gene (TRBV) haplotype and grade 3-4 immune-related adverse events (irAEs) among stage III melanoma patients treated with adjuvant ipilimumab or pembrolizumab. II. To describe the TRBV haplotype distribution among this cohort of patients studied. TRANSLATIONAL MEDICINAL OBJECTIVE RELATED TO ASSOCIATION OF CIRCULATING TUMOR DNA (ctDNA) WITH RELAPSE-FREE SURVIVAL IN HIGH-RISK, RESECTED MELANOMA PATIENTS. I. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms. II. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms. III. To evaluate associations between pretreatment ctDNA and relapse within 2 years of randomization in a case-control analysis within each treatment arm (after treatment arm data are unblinded to investigators). IV. To evaluate associations between "early-on treatment" ctDNA levels and relapse within 2 years of randomization. V. To describe ctDNA levels at end of therapy and time of relapse. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: INDUCTION THERAPY: Patients receive high-dose recombinant interferon alfa-2B intravenously (IV) over 20 minutes on days 1-5. Treatment repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive high-dose recombinant interferon alfa-2B subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, 6 and 12 weeks, every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02506153
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Active, not recruiting
Phase Phase 3
Start date November 10, 2015
Completion date January 23, 2025

See also
  Status Clinical Trial Phase
Recruiting NCT05039801 - IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors Phase 1
Active, not recruiting NCT02224781 - Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma Phase 3
Recruiting NCT05388877 - E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma Phase 1
Active, not recruiting NCT04940299 - Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma Phase 2
Active, not recruiting NCT04967196 - Ipilimumab and Nivolumab for the Treatment of Stage III-IV Unresectable Metastatic Melanoma Phase 1
Active, not recruiting NCT03033576 - Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma Phase 2
Recruiting NCT04697576 - Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma Phase 1
Recruiting NCT05341349 - Stereotactic Radiosurgery and Immune Checkpoint Inhibitors With NovoTTF-100M for the Treatment of Melanoma Brain Metastases Phase 1
Active, not recruiting NCT03816332 - Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers Phase 1
Active, not recruiting NCT04514484 - Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV Phase 1
Recruiting NCT04314401 - National Cancer Institute "Cancer Moonshot Biobank"
Recruiting NCT05764395 - Rigosertib Plus Pembrolizumab in Treating Patients With Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors Phase 2
Not yet recruiting NCT06391099 - Ketogenic Dietary Intervention to Improve Response to Immunotherapy in Patients With Metastatic Melanoma and Metastatic Kidney Cancer N/A
Active, not recruiting NCT03025256 - Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease Phase 1
Active, not recruiting NCT04516122 - Bone Loss in Melanoma Survivors Receiving Immunotherapy
Recruiting NCT05269381 - Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT01989585 - Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma Phase 1/Phase 2
Recruiting NCT06265285 - Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program Phase 2
Recruiting NCT05098210 - Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma or Hormone Receptor Positive Her2 Negative Metastatic Refractory Breast Cancer Phase 1
Completed NCT04067960 - Pharmacogenomics Testing in Directing the Optimal Use of Supportive Care Medications in Patients With Stage III-IV Cancer Early Phase 1