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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Oncothyreon Inc.
ClinicalTrials.gov Identifier:
NCT01616199
First received: June 6, 2012
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Advanced BRAF-mutant Cancers
Drug: PX-866 in combination with vemurafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Oncothyreon Inc.:

Primary Outcome Measures:
  • Incidence and severity of adverse events (phase 1) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) (phase 2) [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma concentrations of PX-866 and metabolites (phase 1) [ Time Frame: 44 days ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR)(phase 2) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Disease Control Rate (DCR)(phase 2) [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Plasma concentrations of vemurafenib (phase 1) [ Time Frame: 44 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 146
Study Start Date: August 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Dose Escalation of PX-866 + vemurafenib Drug: PX-866 in combination with vemurafenib

Phase 1 dose escalation: PX-866 and Vemurafenib administered orally every day in 28-day cycles until progression or unacceptable toxicity.

Phase 2 combination: PX-866 and vemurafenib administered at recommended doses determined from phase 1 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.

Experimental: Phase 2 Combination PX-866 + vemurafenib Drug: PX-866 in combination with vemurafenib

Phase 1 dose escalation: PX-866 and Vemurafenib administered orally every day in 28-day cycles until progression or unacceptable toxicity.

Phase 2 combination: PX-866 and vemurafenib administered at recommended doses determined from phase 1 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.

Active Comparator: Phase 2 Single-agent vemurafenib Drug: PX-866 in combination with vemurafenib

Phase 1 dose escalation: PX-866 and Vemurafenib administered orally every day in 28-day cycles until progression or unacceptable toxicity.

Phase 2 combination: PX-866 and vemurafenib administered at recommended doses determined from phase 1 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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01616199

Locations
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, New York
New York University
New York, New York, United States, 10016
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Oncothyreon Inc.
  More Information

No publications provided

Responsible Party: Oncothyreon Inc.
ClinicalTrials.gov Identifier: NCT01616199     History of Changes
Other Study ID Numbers: PX-866-007
Study First Received: June 6, 2012
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncothyreon Inc.:
PX-866
BRAF-mutant cancers
Advanced melanoma
BRAF inhibitor
Vemurafenib
Zelboraf
PI-3K inhibitor

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 21, 2014