BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma

Phase 1

Completed

Brief Summary: This is a phase 1/2 clinical trial with the goal of determining whether the addition of the investigational agent BKM120 to vemurafenib will lead to improved 6-month progression-free survival in patients with BRAFV600E/K mutant melanoma.

Detailed Description: The phase 1 portion of this trial is a dose escalation study; the phase 2 portion is a single-stage, single arm prospective clinical trial. All patients will receive continuous doses of vemurafenib twice a day and BKM120 once a day.

In the phase 1 portion of the study, there will be a 7 day lead-in period to allow for single dose pharmacokinetic analysis of BKM120 alone. Cycle 1 (28 days) is the dose-limiting toxicity (DLT) period. During phase 1, vemurafenib and BKM120 doses will be escalated using a standard 3+3 dose escalation scheme with the goal of identifying the recommended phase 2 dose.

In the phase 2 portion of the study, patients will receive continuous doses of vemurafenib and BKM120 starting on day 1 of the first cycle. In the phase 2 portion of the study, patients will receive vemurafenib and BKM120 at the recommended phase 2 dose.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
No Previous Treatment	BKM120 Combined with Vemurafenib (PLX4032)	150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events.

Primary Outcome Measures

Name	Time	Method
Phase 1 - Safety & Recommended Phase 2 Dose (RP2D)	28 days	RP2D determined by maximum tolerated dose (MTD), post-dose-limiting toxicity (DLT) period toxicity, and pharmacokinetic data
Phase 2 - Progression-free Survival Rate	6 months	6 month progression-free survival rate (PFS6) determined by tumor assessments, clinical tests and laboratory tests

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome 1 Phase 2 - Objective Response Rate	Day 28 (+/- 3) of even-numbered treatment cycles until progression	Objective response rate determined by tumor assessments, clinical tests and laboratory tests.
Secondary Outcome 4 Phase 2 - Phosphatidylinositol 3-kinase (PI3K)-Pathway Signaling Reduction Levels	No time limit	Greater reduction in PI3K-pathway signaling associated with better PFS determined by laboratory tests and tumor assessments.
Secondary Outcome 6 Phase 2 - MAPK Pathway Gene Expression Levels	No time limit	Responding tumors lack gene expression signatures of MAPK pathway activation, and progressing tumors demonstrate gene expression signatures of MAPK pathway activation - determined by laboratory tests and tumor assessments.
Secondary Outcome 2 Phase 2 - Safety and Tolerability	During study treatment, up to 2 years	Determined by clinical and laboratory tests, and adverse events (AE) assessments
Secondary Outcome 3 Phase 2 - Phosphatase and TENsin (PTEN) Expression	No time limit	PTEN expression associated with better PFS determined by laboratory tests.
Secondary Outcome 5 Phase 2 - PI3K Pathway Gene Expression Levels	No time limit	Responding tumors lack gene expression signatures of PI3K pathway activation, and progressing tumors demonstrate gene expression signatures of PI3K pathway activation - determined by laboratory tests and tumor assessments.

Locations (1): University of California, San Francisco
🇺🇸
San Francisco, California, United States