This trial is active, not recruiting.

Conditions malignant melanoma, colorectal carcinoma
Treatment plx4032
Phase phase 1
Sponsor Plexxikon
Collaborator Roche Pharma AG
Start date November 2006
End date August 2015
Trial size 75 participants
Trial identifier NCT00405587, PLX06-02


The primary objective of this FIH study is to assess the safety and pharmacokinetics of PLX4032 in patients with solid tumors. The secondary objective is to assess the pharmacodynamic activity in paired biopsy specimens obtained from patients with malignant melanoma who have the V600E BRAF oncogenic mutation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Open-label, sequential dose escalation
plx4032 PLX4032
Oral capsules administered BID

Primary Outcomes

Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, ECGs and clinical laboratory tests
time frame: 1 year

Secondary Outcomes

Pharmacodynamic activity in tumor biopsy tissue as assess by paired biopsy (Day 15 vs. Baseline) quantitation of pERK and Ki67
time frame: 3-6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Solid tumors confirmed histologically whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist - Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032 - Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved prior to administration of PLX4032 - Patients in the Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay - ECOG performance status 0 or 1 - Life expectancy ≥ 3 months - Adequate hematologic, hepatic, and renal function Exclusion Criteria: - Brain metastases that are progressing or have been documented to be stable for less than 3 months, or for which systemic corticosteroids are required - Investigational drug use within 28 days of the first dose of PLX4032 - Uncontrolled intercurrent illness - Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption

Additional Information

Official title A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors
Description Activating mutations of the BRAF gene have been observed in a variety of cancers, including 55-68% of malignant melanomas. In general, oncogenic mutations of BRAF correlate with a poor outcome. PLX4032 is a compound that selectively inhibits oncogenic B-Raf kinase. Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Plexxikon.