Phase 1 Study of Patients With Advanced, Unresectable Solid Tumors and Hairy Cell Leukemia Refractory
The study objective is to evaluate the safety and pharmacokinetics (PK) of orally administered PLX8394 in patients with solid tumors. An additional objective is to identify a Recommended Phase 2 (RP2D) for further evaluation in the Extension Cohorts.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced, Unresectable Solid Tumors and Hairy Cell Leukemia Refractory to Standard Therapy|
- Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394 [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]Physical examinations, vital signs, 12-lead electrocardiograms, adverse events, hematology, serum chemistry, and urinalysis will be used to assess safety and tolerability.
- Identification of Recommended Phase 2 dose (RP2D) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
For solid tumor, study drug administration is dosed continuously until clinically significant disease progression, discontinuation of study for any reason or one of the stopping criteria is met.
For hairy cell leukemia, study drug administration is planned for a minimum of 2 cycles (6 weeks) up to a maximum of 8 cycles (6 months).
- If a CR without MRD is achieved at the completion of the initial 2 or 4 cycles, patients will discontinue study drug (End of Study).
- If a CR with MRD, or PR is achieved at the completion of the initial 4 cycles, patients will continue study drug for up to 4 additional cycles (End of Study).
- If there is no response after the initial 4 cycles of study drug, patient will be removed from the study.
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Dose Escalation
300 mg/day PLX8394 cohort 900 mg/day PLX8394
PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF.
Other Name: PLX8394
This will be an open-label, multi-center Phase I/IIa two-part study with a sequential dose escalation part, followed by three parallel Extension cohorts (BRAF-mutated melanoma, BRAF-mutated non-melanoma solid tumors, and BRAF-mutated classical hairy cell leukemia). Up to approximately 42 patients may be enrolled in the dose escalation phase of the study, depending on the number of cohorts required, number of patients per cohort needed, and the need for replacement patients. Approximately 50 patients are planned to be enrolled in the BRAF-mutated tumor Extension cohorts, with the goal of enrolling approximately 10-15 patients with BRAF-mutated hairy cell leukemia, approximately10-15 patients with BRAF mutated anaplastic thyroid carcinoma, approximately 10-15 patients with BRAF mutated papillary carcinoma, and the remainder with other BRAF-mutated solid tumors.
|Contact: Bao Lam, MD||510-647-4008||BLam@plexxikon.com|
|United States, Utah|
|Huntsman Cancer Institute||Not yet recruiting|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Sunil Sharma, MD||Huntsman Cancer Institute|