A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma (CHIR-265-MEL01)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: March 17, 2006
Last updated: October 18, 2013
Last verified: October 2013

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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group 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:

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 [ Time Frame: at the end of dose escalation ] [ Designated as safety issue: No ]

Enrollment: 104
Study Start Date: April 2006
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: July 2014 (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.


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

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

United States, Colorado
University of Colorado Univ.ofColoradoCancerCenter
Aurora, Colorado, United States, 80045
United States, Georgia
Georgia Regents University Cancer Clinical Research Unit
Augusta, Georgia, United States, 30912
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital Dept of Cancer for Melanoma
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute DFCI
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
University of Pennsylvania Health System Dept of Hospital of UnivofPenn
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt University Medical Center Dept. of Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas/MD Anderson Cancer Center StudyCoordinator:CRAF265A2101
Houston, Texas, United States, 77030-4009
Novartis Investigative Site
Zürich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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, 2007-005367-10
Study First Received: March 17, 2006
Last Updated: October 18, 2013
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:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 17, 2014