NCT02079740

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

An Open Label, Two-Part, Phase Ib/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor Trametinib and the BCL2-Family Inhibitor Navitoclax (ABT-263) in Combination in Subjects With KRAS or NRAS Mutation-Positive Advanced Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 96 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies the side effects and best dose of trametinib and navitoclax and how well they work in treating patients with solid tumors that have spread to other places in the body (advanced or metastatic). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax inhibits members of the BCL2 family of proteins that are believed to play key roles in promoting the survival of cancer cells. It may stop the growth of cancer cells by blocking Bcl-2, Bcl-XL, and Bcl-w, proteins needed for cancer cell survival. Giving trametinib and navitoclax may help stop the growth of tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the dose-limiting toxicities of trametinib in combination with navitoclax, and the maximal doses at which both drugs can be safely administered together. (Phase Ib) II. To determine the response rate of the combination of trametinib and navitoclax in subjects with KRAS or NRAS mutation-positive advanced or metastatic solid tumors in disease-specific expansion cohorts. (Phase II) III. To confirm the safety and tolerability of trametinib and navitoclax in combination at the recommended phase 2 dose (RP2D) determined in the Phase 1b portion. (Phase II) SECONDARY OBJECTIVES: I. To determine the pharmacokinetics of both drugs administered together. (Phase Ib) II. To assess for evidence of response to therapy. (Phase Ib) III. To evaluate the pharmacodynamic response to therapy in tumor biopsies. (Phase Ib) IV. To evaluate the pharmacodynamic response to therapy in tumor biopsies (first 15 patients enrolled overall). (Phase II) OUTLINE: This is a phase Ib, dose-escalation study followed by a phase II study. Patients receive trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) every 8 weeks following cycle 1 day 1, biopsy on day 15 or 22 of cycle 1, and collection of blood samples on day 1 of cycles 2, 4, 8, and 12. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Metastatic Malignant Solid Neoplasm
• Refractory Malignant Solid Neoplasm
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo conventional CT or PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Navitoclax	Given PO
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
DRUG	Trametinib	Given PO

Timeline

• Start date: 2014-03-26
• Primary completion: 2022-12-01
• Completion: 2026-03-06
• First posted: 2014-03-06
• Last updated: 2025-09-30
• Results posted: 2025-01-27

Locations

2 sites across 1 country: United States