Trials / Terminated

TerminatedNCT02097225

Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Phase I Study of AT13387 in Combination With Dabrafenib and Trametinib in Patients With BRAF-Mutant Melanoma and Other Solid Tumors

Status: Terminated
Phase: Phase 1
Study type: Interventional
Enrollment: 22 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of onalespib when given together with dabrafenib and trametinib in treating patients with BRAF-mutant melanoma or solid tumors that have spread to another place in the body (metastatic) or cannot be removed by surgery. Onalespib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of onalespib (AT13387) given weekly in combination with dabrafenib and trametinib in patients with BRAF-mutant metastatic or unresectable solid tumors. SECONDARY OBJECTIVES: I. To obtain preliminary estimates of the objective response rate (ORR) and progression-free survival (PFS) and document the 6-month PFS and 1-year overall survival (OS) of patients with BRAF-mutant metastatic or unresectable melanoma treated with AT13387 given weekly in combination with dabrafenib and trametinib. II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and AT13387. OUTLINE: This is a dose-escalation study of onalespib. Four dose levels, plus a fallback dose, are specified in the protocol and are summarized below. The trial is based on a standard 3+3 design with dose escalation beginning in dose level 1 (DL1). In a 3+3 design," three patients are initially enrolled into a given dose cohort. If there is no dose limiting toxicity (DLT) observed in any of these subjects, the trial proceeds to enroll additional subjects into the next higher dose cohort. If one subject develops a DLT at a specific dose, an additional three subjects are enrolled into that same dose cohort. Development of DLTs in more than 1 of 6 subjects in a specific dose cohort suggests that the maximum total dose (MTD) has been exceeded, and further dose escalation is not pursued. Fallback dose level -1 is initiated if more than 1 of 6 subjects in dose level 1 (starting dose) develop DLTs. Patients receive dabrafenib orally (PO) twice daily (BID), trametinib PO once daily (QD) on days 1-28, and onalespib intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dose Level -1 (fallback dose): * Dabrafenib = 75 mg * Trametinib = 1 mg * Onalespib = 180 mg/m\^2 Dose Level 1 (starting dose): * Dabrafenib = 150 mg * Trametinib = 1 mg * Onalespib = 180 mg/m\^2 Dose Level 2: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 180 mg/m\^2 Dose Level 3: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 220 mg/m\^2 Dose Level 4: * Dabrafenib = 150 mg * Trametinib = 2 mg * Onalespib = 260 mg/m\^2 After completion of study treatment, patients are followed up at 28 days and every 6 months for up to 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Dabrafenib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Onalespib	Given IV
OTHER	Pharmacological Study	Correlative studies
DRUG	Trametinib	Given PO

Timeline

Start date: 2014-05-29
Primary completion: 2019-03-31
Completion: 2022-10-26
First posted: 2014-03-27
Last updated: 2024-10-16
Results posted: 2024-10-16

Locations

2 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT02097225. Inclusion in this directory is not an endorsement.