Safety Study of PLX4032 in Patients With Solid Tumors

The recruitment status of this study is unknown because the information has not been verified recently.

Verified October 2009 by Plexxikon. Recruitment status was Active, not recruiting

First Received on November 28, 2006. Last Updated on October 28, 2009 History of Changes

Sponsor:	Plexxikon
Collaborator:	Roche Pharma AG
Information provided by:	Plexxikon
ClinicalTrials.gov Identifier:	NCT00405587

Purpose

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.

The primary objective of this First in Human 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.

Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma.

Condition	Intervention	Phase
Malignant Melanoma Colorectal Carcinoma	Drug: PLX4032	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

U.S. FDA Resources

Further study details as provided by Plexxikon:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	75
Study Start Date:	November 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Oral capsules administered BID

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405587

Locations

United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Royal Melbourne Hospital
Parkville, Victoria, Australia

Sponsors and Collaborators

Plexxikon

Roche Pharma AG

More Information

No publications provided by Plexxikon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15.

Responsible Party:	Keith Nolop, MD, Plexxikon Inc.
ClinicalTrials.gov Identifier:	NCT00405587 History of Changes
Other Study ID Numbers:	PLX06-02
Study First Received:	November 28, 2006
Last Updated:	October 28, 2009
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Carcinoma
Colorectal Neoplasms
Melanoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site

Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on February 09, 2012