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

NCT ID: NCT00304525

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2013-11-30

Brief Summary

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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

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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.

Conditions

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Metastatic Melanoma

Keywords

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Anti-angiogenesis therapy Kinase inhibitor therapy Raf inhibitor Locally Advanced Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RAF265 - Arm 1

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

Group Type EXPERIMENTAL

RAF265

Intervention Type DRUG

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.

RAF265 - Arm 2

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.

Group Type EXPERIMENTAL

RAF265

Intervention Type DRUG

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.

RAF265 - Arm 3

Patients were treated with once weekly dosing of RAF265

Group Type EXPERIMENTAL

RAF265

Intervention Type DRUG

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.

RAF265 - Arm 4

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.

Group Type EXPERIMENTAL

RAF265

Intervention Type DRUG

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.

RAF265 - Arm 5

RAF265 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week.

Group Type EXPERIMENTAL

RAF265

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmeceuticals

Locations

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University of Colorado Univ.ofColoradoCancerCenter

Aurora, Colorado, United States

Site Status

Georgia Regents University Cancer Clinical Research Unit

Augusta, Georgia, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Dept of Cancer for Melanoma

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute DFCI

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)

Boston, Massachusetts, United States

Site Status

University of Pennsylvania Health System Dept of Hospital of UnivofPenn

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center Dept. of Cancer Center

Nashville, Tennessee, United States

Site Status

University of Texas/MD Anderson Cancer Center Onc. Dept,

Houston, Texas, United States

Site Status

Novartis Investigative Site

Zurich, , Switzerland

Site Status

Countries

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Netherlands United States Switzerland

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13806

CRAF265A2101 Results at Novartis Clinical Trial Results Website

Other Identifiers

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2007-005367-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAF265A2101

Identifier Type: -

Identifier Source: org_study_id

NCT00324935

Identifier Type: -

Identifier Source: nct_alias