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A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma
This study is ongoing, but not recruiting participants.

First Received on March 17, 2006.   Last Updated on December 21, 2011   History of Changes
Sponsor: Novartis Pharmaceuticals
Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )
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.

Phase II portion of study (dose expansion) has been cancelled with Amendment 7 as of Dec 2011.


Condition Intervention Phase
Metastatic Melanoma
 Drug: RAF265
 Phase I

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-label, Dose Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RAF265 (CHIR-265)Administered Orally to Patients With Locally Advanced or Metastatic Melanoma.

Resource links provided by NLM:

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: at the end of dose escalation ] [ Designated as safety issue: Yes ]
  • Dose limiting toxicities [ Time Frame: during the PK run-in phase and first cycle (28 day cycle) ] [ Designated as safety issue: Yes ]
  • Safety profile [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
  • Evaluate potential pharmacodynamic effects [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • Pharmacokinetic profile [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • Determine the response rate for BRAF mutant patients [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]
  • Determine the recommended phase two dose - Phase II portion of study (dose expansion) has been cancelled as of Dec 2011. [ Time Frame: at the end of dose escalation ] [ Designated as safety issue: No ]

Enrollment: 104
Study Start Date: April 2006
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAF265 Dose Escalation Drug: RAF265
Experimental: RAF265 - Dose Expansion Drug: RAF265

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:

  1. Confirmed diagnosis of melanoma, locally advanced AJCC Stage IIIB to metastatic Stage IV
  2. 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
  3. ECOG performance status of 0 or 1
  4. No concurrent anticancer or investigational therapy for at least 4 weeks prior to enrollment
  5. No major surgery for at least 4 weeks prior to enrollment

Exclusion Criteria:

  1. Significant cardiac disease or other significant medical/psychiatric disease
  2. History of primary central nervous system tumor or brain metastases onths
  3. History of melena, hematemesis, or hemoptysis within the last 3 months
  4. Previous therapy with certain molecularly targeted agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00304525

Locations
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80217
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Maryland
John Hopkins University
Lutherville, Maryland, United States, 21218
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, United States, 15260
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Switzerland
Novartis Investigative Site
Zurich, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmeceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00304525     History of Changes
Obsolete Identifiers: NCT00324935
Other Study ID Numbers: CRAF265A2101
Study First Received: March 17, 2006
Last Updated: December 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Anti-angiogenesis therapy
Kinase inhibitor therapy
Raf inhibitor
Locally Advanced Melanoma

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 February 09, 2012



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