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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.

Phase 2
18 Years
Open (Enrolling)
Metastatic Melanoma

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Trial Information

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.

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

Inclusion Criteria:

1. Confirmed diagnosis of melanoma, locally advanced AJCC Stage IIIB to metastatic Stage

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

at the end of dose escalation

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

April 2006

Completion Date:

July 2014

Related Keywords:

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



University of Colorado Univ.ofColoradoCancerCenter Aurora, Colorado  80045
Georgia Health Sciences University Cancer Clinical Research Unit Augusta, Georgia  30912
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology Baltimore, Maryland  21231
Massachusetts General Hospital Dept of Cancer for Melanoma Boston, Massachusetts  02114
Dana Farber Cancer Institute DFCI Boston, Massachusetts  02115
Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3) Boston, Massachusetts  02215
University of Pennsylvania Health System Dept of Hospital of UnivofPenn Philadelphia, Pennsylvania  19104
University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center Pittsburgh, Pennsylvania  15232
Vanderbilt University Medical Center Dept. of Cancer Center Nashville, Tennessee  37232
MD Anderson Cancer Center/University of Texas StudyCoordinator:CRAF265A2101 Houston, Texas  77030-4009