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.
18 Years
N/A
Both
Metastatic Melanoma
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
imaging.
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
Type of Study:
Interventional
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:
Yes
Principal Investigator
Novartis Pharmaceuticals
Investigator Role:
Study Director
Investigator Affiliation:
Novartis Pharmaceuticals
Authority:
United States: Food and Drug Administration
Study ID:
CRAF265A2101
NCT ID:
NCT00304525
Start Date:
April 2006
Completion Date:
July 2014
Related Keywords:
- Metastatic Melanoma
- Anti-angiogenesis therapy
- Kinase inhibitor therapy
- Raf inhibitor
- Locally Advanced Melanoma
- Melanoma
Name | Location |
|---|---|
| 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 |
