Clinical Trials Directory

Trials / Active Not Recruiting

Active Not RecruitingNCT01989585

Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma

Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma (Phase I and II) and Other Solid Tumors (Phase I Only)

Status
Active Not Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
75 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with BRAF mutant melanoma or solid tumors that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of tumor cells by blocking Bcl-2, a protein needed for tumor cell survival. Giving navitoclax, dabrafenib, and trametinib may help shrink tumors in patients with melanoma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control dabrafenib and trametinib combination (DT). (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) SECONDARY OBJECTIVES: I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (reverse-phase protein microarrays \[RPPA\]), and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) family gene expression analysis. (Phase II) OUTLINE: This is a phase I, dose-escalation study of dabrafenib, trametinib, and navitoclax followed by a randomized phase II study. PHASE I: Patients receive navitoclax orally (PO) once daily (QD) on days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO twice daily (BID), trametinib PO QD, and navitoclax PO QD days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo electrocardiography (ECHO) or multigated acquisition scan (MUGA), magnetic resonance imaging (MRI) or computed tomography (CT), also undergo biopsy, and collection of blood samples throughout the trial. PHASE II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial. ARM II: Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial. After the completion of study treatment, patients are followed up for clinical evaluation at 28 days and every 3 months thereafter until disease progression or death, whichever comes first. For survival follow up, patients are followed every 12 months for 3 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREComputed TomographyUndergo CT
DRUGDabrafenibGiven PO
PROCEDUREEchocardiography TestUndergo echocardiography
OTHERLaboratory Biomarker AnalysisCorrelative studies
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREMultigated Acquisition ScanUndergo multigated acquisition scan
BIOLOGICALNavitoclaxGiven PO
OTHERPharmacological StudyCorrelative studies
DRUGTrametinibGiven PO

Timeline

Start date
2014-03-24
Primary completion
2027-12-31
Completion
2027-12-31
First posted
2013-11-21
Last updated
2026-04-13

Locations

49 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT01989585. Inclusion in this directory is not an endorsement.