BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma
|BRAF Mutant Metastatic Melanoma||Drug: BKM120 Combined with Vemurafenib (PLX4032)||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 1/2 Trial of BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma (Novartis Study Number CBKM120ZUS21T)|
- Phase 1 - Safety & Recommended Phase 2 Dose (RP2D) [ Time Frame: 28 days ]RP2D determined by MTD, post-DLT period toxicity, and pharmacokinetic data
- Phase 2 - Progression-free survival rate [ Time Frame: 6 months ]6 month progression-free survival rate (PFS6) determined by tumor assessments, clinical tests and laboratory tests
- Secondary Outcome 1 Phase 2 - Response Rates [ Time Frame: Day 28 (+/- 3) of even-numbered treatment cycles until progression ]Objective response rate, (ORR = CR + PR), PFS and OS determined by tumor assessments, clinical tests and laboratory tests
- Secondary Outcome 2 Phase 2 - Safety and Tolerability [ Time Frame: During study treatment, up to 2 years ]Determined by clinical and laboratory tests, and AE assessments
- Secondary Outcome 3 Phase 2 - PTEN expression [ Time Frame: No time limit ]PTEN expression associated with better PFS determined by laboratory tests
- Secondary Outcome 4 Phase 2 - PI3K-pathway signaling [ Time Frame: No time limit ]Greater reduction in PI3K-pathway signaling associated with better PFS determined by laboratory tests and tumor assessments
- Secondary Outcome 5 Phase 2 - PI3K and MAPK expression [ Time Frame: No time limit ]Responding tumors lack gene expression signatures of both PI3K and MAPK pathway activation, and progressing tumors demonstrate gene expression signatures of either PI3K or MAPK pathway activation - determined by laboratory tests and tumor assessments
|Actual Study Start Date:||June 9, 2012|
|Study Completion Date:||March 21, 2017|
|Primary Completion Date:||December 13, 2013 (Final data collection date for primary outcome measure)|
No Previous Treatment
150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events.
Drug: BKM120 Combined with Vemurafenib (PLX4032)
Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)
Dose Level -1: BKM120 60 mg daily, Vemurafenib 480 mg bid
Dose Level 1: BKM120 60 mg daily, Vemurafenib 720 mg bid
Dose Level 2: BKM120 80 mg daiy, Vemurafenib 720 mg bid
Dose Level 3: BKM120 100 mg daiy, Vemurafenib 720 mg bid
Dose Level 4: BKM120 100 mg daiy, Vemurafenib 960 mg bid
Phase II is a single-stage, single arm prospective trial: patients will receive BKM120 and vemurafenib at the RP2D
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01512251
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|