NCT01616199

Study of PX-866 and Vemurafenib in Patients With Advanced Melanoma

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Cascadian Therapeutics Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Advanced BRAF-mutant Cancers

Interventions

Type	Name	Description
DRUG	PX-866	Phase 1 dose escalation: PX-866 in combination administered orally every day in 28-day cycles until progression or unacceptable toxicity. Phase 2 combination: PX-866 and vemurafenib administered every day in 28 day cycles until progression or unacceptable toxicity. Phase 2 single-agent: vemurafenib administered orally at labeled dose every day in 28 day cycles until progression or unacceptable toxicity.
DRUG	vemurafenib	vemurafenib is a B-Raf enzyme inhibitor

Timeline

• Start date: 2012-08-01
• Primary completion: 2014-12-01
• Completion: 2015-03-01
• First posted: 2012-06-11
• Last updated: 2018-05-16

Locations

5 sites across 1 country: United States