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

Primary Purpose

Metastatic Melanoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RAF265
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring Anti-angiogenesis therapy, Kinase inhibitor therapy, Raf inhibitor, Locally Advanced Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 History of melena, hematemesis, or hemoptysis within the last 3 months Previous therapy with certain molecularly targeted agents

Sites / Locations

  • University of Colorado Univ.ofColoradoCancerCenter
  • Georgia Regents University Cancer Clinical Research Unit
  • Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
  • Massachusetts General Hospital Dept of Cancer for Melanoma
  • Dana Farber Cancer Institute DFCI
  • Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)
  • University of Pennsylvania Health System Dept of Hospital of UnivofPenn
  • University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center
  • Vanderbilt University Medical Center Dept. of Cancer Center
  • University of Texas/MD Anderson Cancer Center Onc. Dept,
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

RAF265 - Arm 1

RAF265 - Arm 2

RAF265 - Arm 3

RAF265 - Arm 4

RAF265 - Arm 5

Arm Description

Patients received 10mg RAF265 as a once weekly dose until progressive disease was confirmed.

RAF265 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.

Patients were treated with once weekly dosing of RAF265

Patients 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 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week.

Outcomes

Primary Outcome Measures

Maximum tolerated dose
Dose limiting toxicities
Safety profile
Evaluate potential pharmacodynamic effects
Pharmacokinetic profile

Secondary Outcome Measures

Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response
Determine the response rate for BRAF mutant patients
Determine the recommended phase two dose

Full Information

First Posted
March 17, 2006
Last Updated
December 11, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00304525
Brief Title
A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma
Acronym
CHIR-265-MEL01
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma
Keywords
Anti-angiogenesis therapy, Kinase inhibitor therapy, Raf inhibitor, Locally Advanced Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAF265 - Arm 1
Arm Type
Experimental
Arm Description
Patients received 10mg RAF265 as a once weekly dose until progressive disease was confirmed.
Arm Title
RAF265 - Arm 2
Arm Type
Experimental
Arm Description
RAF265 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.
Arm Title
RAF265 - Arm 3
Arm Type
Experimental
Arm Description
Patients were treated with once weekly dosing of RAF265
Arm Title
RAF265 - Arm 4
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
RAF265 - Arm 5
Arm Type
Experimental
Arm Description
RAF265 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week.
Intervention Type
Drug
Intervention Name(s)
RAF265
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Time Frame
at the end of dose escalation
Title
Dose limiting toxicities
Time Frame
during the PK run-in phase and first cycle (28 day cycle)
Title
Safety profile
Time Frame
throughout the study
Title
Evaluate potential pharmacodynamic effects
Time Frame
throughout the study
Title
Pharmacokinetic profile
Time Frame
throughout the study
Secondary Outcome Measure Information:
Title
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
Title
Determine the response rate for BRAF mutant patients
Time Frame
Every 2 months
Title
Determine the recommended phase two dose
Time Frame
at the end of dose escalation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 History of melena, hematemesis, or hemoptysis within the last 3 months Previous therapy with certain molecularly targeted agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmeceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado Univ.ofColoradoCancerCenter
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgia Regents University Cancer Clinical Research Unit
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Massachusetts General Hospital Dept of Cancer for Melanoma
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute DFCI
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Pennsylvania Health System Dept of Hospital of UnivofPenn
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt University Medical Center Dept. of Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas/MD Anderson Cancer Center Onc. Dept,
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Novartis Investigative Site
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13806
Description
CRAF265A2101 Results at Novartis Clinical Trial Results Website

Learn more about this trial

A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma

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