Advanced BRAF-mutant Cancers Clinical Trial
Official title:
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
The purpose of the phase 1 portion of the study is to determine the maximally tolerated dose
(MTD) or recommended dose (RD) and the safety/tolerability of PX-866 in combination
vemurafenib in patients with any advanced BRAF-mutant cancer.
The purpose of the phase 2 portion of the study is to compare progression free survival
(PFS), antitumor activity (response rate), disease control rate (DCR), and the safety and
tolerability of PX-866 in combination with vemurafenib vs. vemurafenib alone in patients with
advanced BRAF-mutant melanoma at the doses recommended from Phase 1.
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.
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