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Report for Clinical Trial NCT01616199

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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.

NCT01616199 Advanced BRAF-mutant Cancers
MeSH:Melanoma
HPO:Cutaneous melanoma Melanoma

2 Interventions

Name: PX-866

Description: 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.
Type: Drug
Group Labels: 2

Phase 1 Dose Escalation of PX-866 + vemurafenib Phase 2 Combination PX-866 + vemurafenib

Name: vemurafenib

Description: vemurafenib is a B-Raf enzyme inhibitor
Type: Drug
Group Labels: 3

Phase 1 Dose Escalation of PX-866 + vemurafenib Phase 2 Combination PX-866 + vemurafenib Phase 2 Single-agent vemurafenib


Primary Outcomes

Measure: Incidence and severity of adverse events (phase 1)

Time: 28 days

Measure: Progression-free survival (PFS) (phase 2)

Time: 56 days

Secondary Outcomes

Measure: Plasma concentrations of PX-866 and metabolites (phase 1)

Time: 44 days

Measure: Objective Response Rate (ORR)(phase 2)

Time: 56 days

Measure: Disease Control Rate (DCR)(phase 2)

Time: 56 Days

Measure: Plasma concentrations of vemurafenib (phase 1)

Time: 44 days

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 V600E

Inclusion Criteria: - ≥ 18 years at time of consent - If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug - If female of child-bearing potential, negative pregnancy test - For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. --- V600E ---

For Phase 2: must have histologically or cytologically-confirmed BRAF mutation-positive (V600E or V600K) advanced (defined as unresectable Stage IIIC or IV) melanoma that has not been treated with a selective BRAF inhibitor - For Phase 1: must have measurable or non-measurable disease. --- V600E ---

These patients must have undergone appropriate imaging studies and currently be on a stable, lowest possible dose of steroids - History of allergic reactions attributed to compounds of similar chemical or biologic composition to PX-866 or vemurafenib - Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Uncorrectable electrolyte abnormalities or long QT syndrome - Poorly controlled diabetes mellitus - Pregnant, breastfeeding, or planning to become pregnant - Known to be human immunodeficiency virus (HIV)-positive - Inability to swallow pills - Previous treatment with a phosphatidylinositol-3-kinase (PI-3K) inhibitor - Any other significant medical or psychiatric condition that in the opinion of the investigator renders the patient inadequate for participation Inclusion Criteria: - ≥ 18 years at time of consent - If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug - If female of child-bearing potential, negative pregnancy test - For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. --- V600E ---


2 V600K

Inclusion Criteria: - ≥ 18 years at time of consent - If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug - If female of child-bearing potential, negative pregnancy test - For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. --- V600E --- --- V600K ---

For Phase 2: must have histologically or cytologically-confirmed BRAF mutation-positive (V600E or V600K) advanced (defined as unresectable Stage IIIC or IV) melanoma that has not been treated with a selective BRAF inhibitor - For Phase 1: must have measurable or non-measurable disease. --- V600E --- --- V600K ---

These patients must have undergone appropriate imaging studies and currently be on a stable, lowest possible dose of steroids - History of allergic reactions attributed to compounds of similar chemical or biologic composition to PX-866 or vemurafenib - Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Uncorrectable electrolyte abnormalities or long QT syndrome - Poorly controlled diabetes mellitus - Pregnant, breastfeeding, or planning to become pregnant - Known to be human immunodeficiency virus (HIV)-positive - Inability to swallow pills - Previous treatment with a phosphatidylinositol-3-kinase (PI-3K) inhibitor - Any other significant medical or psychiatric condition that in the opinion of the investigator renders the patient inadequate for participation Inclusion Criteria: - ≥ 18 years at time of consent - If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug - If female of child-bearing potential, negative pregnancy test - For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. --- V600E --- --- V600K ---



HPO Nodes


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