Trials / Active Not Recruiting

Active Not RecruitingNCT02910700

Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma

A Phase II Study of the TRIplet Combination of Dabrafenib, Nivolumab, and Trametinib in Patients With Metastatic Melanoma (TRIDeNT) or Binimetinib, EnCorafenib, and NivolumAb (TRIBECA)

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 52 (actual)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies the side effects and how well nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib work in treating patients with BRAF-mutated stage III-IV melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Trametinib, dabrafenib, encorafenib, and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib may work better in treating patients with BRAF-mutated melanoma.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety, tolerability, and efficacy (objective response rates by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) of nivolumab in combination with dabrafenib and trametinib or encorafenib and binimetinib in patients with BRAF-mutated metastatic melanoma. SECONDARY OBJECTIVES: I. Safety and tolerability of the nivolumab, dabrafenib, and trametinib triplet combination (NDT). II. Safety and tolerability of the nivolumab, binimetinib and encorafenib. III. Efficacy of the combination as measured by the depth and duration of response by RECIST 1.1 and modified RECIST 1.1 (to include intracranial response). IV. Pharmacodynamic evaluation of combination on circulating markers (immune monitoring). V. Pharmacodynamic evaluation of combination on tumor tissues. VI. Progression- free survival and overall survival. OUTLINE: Patients are assigned to 1 of 3 arms. ARM A (NDT, CLOSED): Patients receive nivolumab intravenously (IV) over 30 minutes on day 1, dabrafenib orally (PO) twice daily (BID) on days 1-28, and trametinib PO once daily (QD) on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. ARM B (NT, CLOSED TO ACCRUAL): Patients receive nivolumab IV over 30 minutes on day 1 and 15, and trametinib PO QD on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. ARM C (NEB): Patients receive nivolumab IV over 30 minutes on day 1 and 15, encorafenib PO QD on days 1-28, and binimetinib PO BID on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days then every 3 months for up to 3 years.

Conditions

Interventions

Type	Name	Description
DRUG	Binimetinib	Given PO
DRUG	Dabrafenib	Given PO
DRUG	Encorafenib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Nivolumab	Given IV
OTHER	Pharmacological Study	Correlative studies
DRUG	Trametinib	Given PO

Timeline

Start date: 2016-12-09
Primary completion: 2027-12-08
Completion: 2027-12-08
First posted: 2016-09-22
Last updated: 2025-12-17

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02910700. Inclusion in this directory is not an endorsement.