A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma
CHIR-265-MEL01
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.
2 other identifiers
interventional
104
2 countries
11
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2006
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2006
CompletedFirst Posted
Study publicly available on registry
March 20, 2006
CompletedStudy Start
First participant enrolled
April 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2013
CompletedDecember 19, 2020
August 1, 2020
7.6 years
March 17, 2006
December 11, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Maximum tolerated dose
at the end of dose escalation
Dose limiting toxicities
during the PK run-in phase and first cycle (28 day cycle)
Safety profile
throughout the study
Evaluate potential pharmacodynamic effects
throughout the study
Pharmacokinetic profile
throughout the study
Secondary Outcomes (3)
Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response
throughout the study
Determine the response rate for BRAF mutant patients
Every 2 months
Determine the recommended phase two dose
at the end of dose escalation
Study Arms (5)
RAF265 - Arm 1
EXPERIMENTALPatients received 10mg RAF265 as a once weekly dose until progressive disease was confirmed.
RAF265 - Arm 2
EXPERIMENTALRAF265 is given as a single "PK run-in" dose, a single loading dose on day 1 of cycle 1, followed by once daily maintenance doses.
RAF265 - Arm 3
EXPERIMENTALPatients were treated with once weekly dosing of RAF265
RAF265 - Arm 4
EXPERIMENTALPatients with locally advanced or metastatic melanoma will utilize a dose close to or at the MTD/RPTD of the liquid formulation that was determined in Arm 2.
RAF265 - Arm 5
EXPERIMENTALRAF265 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week.
Interventions
A liquid nonaqueous oral formulation. Switched to a tablet formulations with was 60% bioavailable, relative to the liquid at 50mg dose. The liquid dose will be multiplied by a factor of 1.67 to achieve a comparable tablet dose. Tablets are available in 10mg and 50mg strengths.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Significant cardiac disease or other significant medical/psychiatric disease
- History of primary central nervous system tumor or brain metastases
- History of melena, hematemesis, or hemoptysis within the last 3 months
- Previous therapy with certain molecularly targeted agents
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
University of Colorado Univ.ofColoradoCancerCenter
Aurora, Colorado, 80045, United States
Georgia Regents University Cancer Clinical Research Unit
Augusta, Georgia, 30912, United States
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
Baltimore, Maryland, 21231, United States
Massachusetts General Hospital Dept of Cancer for Melanoma
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute DFCI
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)
Boston, Massachusetts, 02215, United States
University of Pennsylvania Health System Dept of Hospital of UnivofPenn
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt University Medical Center Dept. of Cancer Center
Nashville, Tennessee, 37232, United States
University of Texas/MD Anderson Cancer Center Onc. Dept,
Houston, Texas, 77030-4009, United States
Novartis Investigative Site
Zurich, 8091, Switzerland
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmeceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2006
First Posted
March 20, 2006
Study Start
April 1, 2006
Primary Completion
November 1, 2013
Study Completion
November 1, 2013
Last Updated
December 19, 2020
Record last verified: 2020-08