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.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00304525
First received: March 17, 2006
Last updated: September 28, 2012
Last verified: September 2012
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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 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 ]
| Estimated Enrollment: | 170 |
| Study Start Date: | April 2006 |
| Estimated Study Completion Date: | July 2014 |
| 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.
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 AJCC Stage IIIB to 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
- History of primary central nervous system tumor or brain metastases onths
- 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
Locations
| United States, Colorado | |
| University of Colorado Univ.ofColoradoCancerCenter | |
| Aurora, Colorado, United States, 80045 | |
| United States, Georgia | |
| Georgia Health Sciences 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 | |
| MD Anderson Cancer Center/University of Texas StudyCoordinator:CRAF265A2101 | |
| Houston, Texas, United States, 77030-4009 | |
| Switzerland | |
| Novartis Investigative Site | |
| Zürich, Switzerland, 8091 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| 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: | September 28, 2012 |
| 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 May 23, 2013