Phase 1/2 Study of PI-3K Inhibition With PX-866 Combined With Vemurafenib (BRAF Inhibitor) in Patients With BRAF-mutant Cancer Including Advanced Melanoma
This is a Phase 1 / 2 open-label study of PX-866 given in combination with vemurafenib to
patients with BRAF-mutant cancer, including advanced melanoma.
Phase 1 will use a 3+3 dose escalation design to evaluate up to three dose levels of PX-866
in combination with up to two dose levels of vemurafenib in order to identify the maximal
tolerated dose/recommended dose (MTD/RD) of both PX-866 and vemurafenib to be used in Phase
2. Vemurafenib will be administered orally twice per day on days 1-28 of all cycles except
cycle 1, where vemurafenib will be administered on days 9-28 to allow for PK assessments).
PX-866 will be administered once per day on days 1-28 of each cycle.
Phase 2 will evaluate the antitumor activity and safety of PX-866 given to patients
randomized 2:1 to receive combination with vemurafenib at the doses recommended from Phase 1
compared with vemurafenib alone administered at the approved dose orally BID. All
treatments will be administered on a 28-day cycle.
Patients randomized to receive single-agent vemurafenib may cross-over to receive the
combination treatment at the time of progression. Patients will be evaluated for progression
approximately every 8 weeks for the initial 24 weeks and every 12 weeks thereafter. All
patients with stable disease (SD) or better, will receive repeat cycles until disease
progression (PD), unacceptable toxicity, or withdrawal of consent.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence and severity of adverse events (phase 1)
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|H. Lee Moffitt Cancer Center||Tampa, Florida 33612|
|New York University||New York, New York 10016|