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

Metastatic Melanoma Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304525
• Other study ID #: CRAF265A2101
• Secondary ID: 2007-005367-10
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2006
• Est. completion date: November 2013

Study information

• Verified date: August 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00324935

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

3. History of melena, hematemesis, or hemoptysis within the last 3 months

4. Previous therapy with certain molecularly targeted agents

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• RAF265
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.

Locations

Country	Name	City	State
Switzerland	Novartis Investigative Site	Zürich
United States	Georgia Regents University Cancer Clinical Research Unit	Augusta	Georgia
United States	University of Colorado Univ.ofColoradoCancerCenter	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)	Boston	Massachusetts
United States	Dana Farber Cancer Institute DFCI	Boston	Massachusetts
United States	Massachusetts General Hospital Dept of Cancer for Melanoma	Boston	Massachusetts
United States	University of Texas/MD Anderson Cancer Center Onc. Dept,	Houston	Texas
United States	Vanderbilt University Medical Center Dept. of Cancer Center	Nashville	Tennessee
United States	University of Pennsylvania Health System Dept of Hospital of UnivofPenn	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose		at the end of dose escalation
Primary	Dose limiting toxicities		during the PK run-in phase and first cycle (28 day cycle)
Primary	Safety profile		throughout the study
Primary	Evaluate potential pharmacodynamic effects		throughout the study
Primary	Pharmacokinetic profile		throughout the study
Secondary	Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response		throughout the study
Secondary	Determine the response rate for BRAF mutant patients		Every 2 months
Secondary	Determine the recommended phase two dose		at the end of dose escalation

External Links

•   CRAF265A2101 Results at Novartis Clinical Trial Results Website