A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma - Full Text View

Sponsored by:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00304525

Purpose

The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of RAF265 in patients with locally advanced and metastatic melanoma.

Condition	Intervention	Phase
Metastatic Melanoma	Drug: RAF265	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RAF265 Administered Orally to Subjects With Locally Advanced or Metastatic Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Maximum tolerated dose
Dose limiting toxicities
Safety profile
Evaluate potential pharmacodynamic effects

Secondary Outcome Measures:

Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response
Determine the overall tumor response
Determine the optimal biologic dose

Estimated Enrollment:	198
Study Start Date:	April 2006

Detailed Description:

The Ras/Raf/MEK/ERK pathway plays a prominent role in controlling several key cellular functions including growth, proliferation and survival. B-Raf is a member of the Ras/Raf/MEK/ERK pathway and is frequently mutated in melanoma resulting in activation of the MAPK pathway. RAF265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.

The primary objectives of this study are to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and the safety profile of RAF265 when administered orally to subjects with locally advanced or metastatic melanoma; to determine the plasma pharmacokinetics (PKs) of orally administered RAF265; and to evaluate potential pharmacodynamic effects of RAF265 using tumor biopsies, peripheral blood samples, and tumor imaging.

Eligibility

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

Criteria

Inclusion Criteria:

Confirmed diagnosis of melanoma, locally advanced Stage IIIC or metastatic Stage IV
Measurable disease - at least one lesion measured in at least one dimension as ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan
ECOG performance status of 0 or 1
No concurrent anticancer or investigational therapy for at least 4 weeks prior to enrollment
No major surgery for at least 4 weeks prior to enrollment

Exclusion Criteria:

Significant cardiac disease or other significant medical/psychiatric disease
Known central nervous system metastases controlled for ≤ 3 months
History of melena, hematemesis, or hemoptysis within the last 3 months
Previous therapy with certain molecularly targeted agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00304525

Contacts

Contact: Novartis

1 800 340 6843

Locations

United States, Georgia
Medical College of Georgia	Not yet recruiting
Augusta, Georgia, United States, 30912
Contact: Rosemary Chandler 706-721-0211 rchandler@mcg.edu
Principal Investigator: Amanda May, M.D.
United States, Maryland
John Hopkins University	Recruiting
Lutherville, Maryland, United States, 21218
Contact: JoAnn Santymer, R.N. 410-516-8000 isantmy1@jhmi.edu
Principal Investigator: William Sharfman, M.D.
United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Christine Byrnes cbyrnes@bidmc.harvard.edu
Principal Investigator: Michael Atkins, M.D.
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Suzanne MacRae 617-632-5906 Suzanne_mac_rae@dfci.harvard.edu
Principal Investigator: F. Stephen Hodi, M.D.
Massachusetts Generla Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Elizabeth Howe 617-726-2000 ehowe@partners.org
Principal Investigator: Donald Lawrence, M.D.
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maryann Gallagher, RN maryann.gallagher@uphs.upenn.edu
Principal Investigator: Keith Flaherty, M.D.
University of Pittsburg Medical Center	Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15260
Contact: Maggie Soncini 412-624-4141 sonciniml@upmc.edu
Principal Investigator: Ahmad Tarhini, M.D.
United States, Tennessee
Vanderbilt Ingram Cancer Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Peggy Krozely, R.N. 615-936-5847 peggy.krozely@vanderbilt.edu
Principal Investigator: Igor Puzanov, M.D
United States, Texas
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Suzanne Lawrence, R.N., BSN slawrenc@mdanderson.org
Principal Investigator: Kevin Kim, M.D.
Institute for Drug Development Cancer Therapy & Research Center at UTHSCSA	Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: John Sarantopoulos, M.D. 210-450-1000
Principal Investigator: John Sarantopoulos, M.D.
Switzerland
Novartis Investigative Site	Recruiting
Zurich, Switzerland

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis Pharmaceuticals

Novartis Pharmeceuticals

More Information

No publications provided

Responsible Party:	Novartis ( External Affairs )
Study ID Numbers:	CRAF265A2101
Study First Received:	March 17, 2006
Last Updated:	April 9, 2009
ClinicalTrials.gov Identifier:	NCT00304525 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Anti-angiogenesis therapy
Kinase inhibitor therapy
Raf inhibitor
Locally Advanced Melanoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Nevus
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue
Nevi and Melanomas
Neuroendocrine Tumors
Melanoma

ClinicalTrials.gov processed this record on August 24, 2009