Ignite Creation Date:
2025-12-26 @ 12:14 PM
Ignite Modification Date:
2026-01-13 @ 9:01 AM
Study NCT ID:
NCT02910700
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-17
First Post:
2016-09-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
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
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: