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

Conditions

• Clinical Stage III Cutaneous Melanoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Metastatic Melanoma
• Recurrent Melanoma
• Unresectable Melanoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Computed Tomography — PROCEDURE
  Undergo CT
• Dabrafenib Mesylate — DRUG
  Given PO
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Ipilimumab — BIOLOGICAL
  Given IV
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA scan
• Nivolumab — BIOLOGICAL
  Given IV
• Quality-of-Life Assessment — OTHER
  Ancillary studies
• Trametinib Dimethyl Sulfoxide — DRUG
  Given PO

Study Details

This phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as BRAFV600 and cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.

Key Dates

Start date

Sep 8, 2015

Status verified

Jan 2026

Primary completion

Sep 30, 2023

Completion

Dec 19, 2026

Study Design

Enrollment

267 participants (actual)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Experimental: Arm A (immunotherapy)
  IMMUNOTHERAPY INDUCTION (CYCLES 1-2): Patients receive nivolumab IV over 30-60 minutes and ipilimumab IV over 30-90 minutes on days 1 and 22. Treatment repeats every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. IMMUNOTHERAPY MAINTENANCE (CYCLES 3-14): Patients receive nivolumab IV over 30-60 minutes on days 1, 15, and 29. Treatment repeats every 6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Upon disease progression (or before), patients re-register and cross over to Arm C. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.
• Experimental: Arm B (BRAF inhibitor therapy)
  Patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO daily on days 1-42. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression (or before), patients re-register and cross over to Arm D. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.
• Experimental: Arm C (BRAF inhibitor therapy)
  Patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO daily on days 1-42. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.
• Experimental: Arm D (immunotherapy)
  IMMUNOTHERAPY INDUCTION (CYCLES 1-2): Patients receive nivolumab IV over 30-60 minutes and ipilimumab IV over 30-90 minutes on days 1 and 22. Treatment repeats every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. IMMUNOTHERAPY MAINTENANCE (CYCLES 3-14): Patients receive nivolumab IV over 30-60 minutes on days 1, 15, and 29. Treatment repeats every 6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.

Primary Outcome Measure

2-year Overall Survival (OS) [ Time Frame: assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry ]

Locations (840)

Related coverage on Hipa.ai

• Nivolumab-based Immunotherapy Shows Improved 2-Year OS in BRAFV600 Melanoma
  Nivolumab · Feb 18, 2026 · ClinicalTrials.gov
• Nivolumab Combo Shows Improved 2-Year OS in BRAFV600 Melanoma Phase 3 Trial
  Nivolumab · Sep 30, 2023 · ClinicalTrials.gov

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