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

NCT01616199 | Terminated Phase 1 DMC

• 1 other identifier: PX-866-007
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Advanced BRAF-mutant Cancers

Keywords

PX-866; BRAF-mutant cancers; Advanced melanoma; BRAF inhibitor; Vemurafenib; Zelboraf; PI-3K inhibitor

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events (phase 1)

  28 days

• Progression-free survival (PFS) (phase 2)

  56 days

Secondary Outcomes (4)

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

  44 days

• Objective Response Rate (ORR)(phase 2)

  56 days

• Disease Control Rate (DCR)(phase 2)

  56 Days

• Plasma concentrations of vemurafenib (phase 1)

  44 days

Study Arms (3)

Phase 1 Dose Escalation of PX-866 + vemurafenib

EXPERIMENTAL

PX-866 given with vemurafenib

Drug: PX-866; Drug: vemurafenib

Phase 2 Combination PX-866 + vemurafenib

EXPERIMENTAL

PX-866 given with vemurafenib

Drug: PX-866; Drug: vemurafenib

Phase 2 Single-agent vemurafenib

ACTIVE COMPARATOR

vemurafenib given as a single agent

Drug: vemurafenib

Interventions

PX-866 DRUG

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.

Also known as: PI-3K inhibitor

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

vemurafenib DRUG

vemurafenib is a B-Raf enzyme inhibitor

Also known as: Zelboraf

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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. Patients must have disease sites amenable to biopsy. 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. For Phase 2: must have measurable disease per RECIST 1.1
• For Phase 1: no restriction on number of prior therapy regimens. For Phase 2: the following restrictions on prior therapy apply: 1) must not have been treated with a selective BRAF inhibitor and must not have had more than 2 prior treatment regimens for advanced metastatic disease; 2) must have completed prior cytotoxic chemotherapy a minimum of 4 weeks prior to starting PX-866 and/or vemurafenib (except for BCNU and/or mitomycin C, which must have been completed a minimum of 6 weeks prior to starting therapy). Prior biologic therapy and localized radiation therapy must have been completed a minimum of 2 weeks prior to starting therapy.
• All toxicities related to prior cancer therapies other than alopecia must have resolved to Grade 1 or less
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• In the opinion of the clinical investigator, life expectancy \> 3 months
• Adequate hematologic function
• Adequate hepatic function
• Serum creatinine \< 2.0 mg/dL
• Adequate cardiac function
• Corrected QTc must be \<480 milliseconds

You may not qualify if:

• May not be receiving any other investigational agents
• Active central nervous system (CNS) metastases are excluded. Patients with a history of CNS metastasis, who have been treated prior to enrollment, must be stable for eight weeks after completion of treatment. 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

Sponsors & Collaborators

• Cascadian Therapeutics Inc.: lead

Study Sites (5)

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

New York University

New York, New York, 10016, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

PX-866; Vemurafenib

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 11, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: March 1, 2015
• Last Updated: May 16, 2018

Record last verified: 2015-07

Locations

US (5)