A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers

NCT ID: NCT01524978

Last Updated: 2017-11-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-12

Study Completion Date

2016-10-28

Brief Summary

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This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.

Detailed Description

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Conditions

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Multiple Myeloma, Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib

Participants with NSCLC will be treated with vemurafenib monotherapy.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Cohort 2: Ovarian Cancer - vemurafenib

Participants with ovarian cancer will be treated with vemurafenib monotherapy.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Cohort 3a: Colorectal Cancer - vemurafenib

Participants with colorectal cancer will be treated with vemurafenib monotherapy.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab

Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy.

Group Type EXPERIMENTAL

cetuximab

Intervention Type DRUG

Escalating doses administered on Day 1 and then once weekly by intravenous infusion.

vemurafenib

Intervention Type DRUG

Escalating doses given orally twice a day starting on Day 2

Cohort 4: Cholangiocarcinoma - vemurafenib

Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Cohort 6: Multiple Myeloma - vemurafenib

Participants with multiple myeloma will be treated with vemurafenib monotherapy.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Cohort 7: Other Solid Tumors - vemurafenib

Participants with Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), anaplastic thyroid cancer, advanced stage astrocytoma, early stage astrocytoma and other BRAF V600-positive tumors will be treated with vemurafenib monotherapy. Subcohorts will be analyzed separately if 7 or more participants are enrolled for each indication.

Group Type EXPERIMENTAL

vemurafenib

Intervention Type DRUG

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Interventions

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cetuximab

Escalating doses administered on Day 1 and then once weekly by intravenous infusion.

Intervention Type DRUG

vemurafenib

Escalating doses given orally twice a day starting on Day 2

Intervention Type DRUG

vemurafenib

960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.

Intervention Type DRUG

Other Intervention Names

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Zelboraf Zelboraf

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Must have recovered from all side effects of their most recent systemic or local treatment
* Adequate hematological, renal and liver function

For solid tumors only:

* Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
* Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)

For multiple myeloma only:

* Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
* Must have received at least one prior systemic therapy for the treatment of multiple myeloma
* Treated with local radiotherapy
* Must have relapsed and/or refractory multiple myeloma with measurable disease

Exclusion Criteria

* Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
* Uncontrolled concurrent malignancy
* Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
* Active or untreated central nervous system (CNS) metastases
* History of or known carcinomatous meningitis
* Concurrent administration of any anti-cancer therapies other than those administered in this study
* Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Arizona Oncology

Tucson, Arizona, United States

Site Status

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, United States

Site Status

Massachusetts General Hospital;Oncology

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Vanderbilt

Nashville, Tennessee, United States

Site Status

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

Site Status

Tianjin Cancer Hospital

Tianjin, , China

Site Status

Institut Bergonie; Oncologie

Bordeaux, , France

Site Status

Centre Francois Baclesse; Oncologie

Caen, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Site Status

Institut Paoli-Calmettes; Oncologie Medicale 1

Marseille, , France

Site Status

Centre Rene Gauducheau

Saint-Herblain, , France

Site Status

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

Site Status

Institut Gustave Roussy; Sitep

Villejuif, , France

Site Status

Klinik der Uni zu Koeln; Klinik I für Innere Medizin; Onkologie

Cologne, , Germany

Site Status

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

Essen, , Germany

Site Status

Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum

Mannheim, , Germany

Site Status

Hospital Univ. Central de Asturias; Servicio de Oncologia

Oviedo, Principality of Asturias, Spain

Site Status

Hospital del Mar; Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Site Status

Fundacion Jimenez Diaz; Servicio de Oncologia

Madrid, , Spain

Site Status

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

Salamanca, , Spain

Site Status

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

The Royal Marsden Hospital; Dept of Medicine

London, , United Kingdom

Site Status

The Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States China France Germany Spain United Kingdom

References

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Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.

Reference Type DERIVED
PMID: 37934000 (View on PubMed)

Kaley T, Touat M, Subbiah V, Hollebecque A, Rodon J, Lockhart AC, Keedy V, Bielle F, Hofheinz RD, Joly F, Blay JY, Chau I, Puzanov I, Raje NS, Wolf J, DeAngelis LM, Makrutzki M, Riehl T, Pitcher B, Baselga J, Hyman DM. BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study. J Clin Oncol. 2018 Dec 10;36(35):3477-3484. doi: 10.1200/JCO.2018.78.9990. Epub 2018 Oct 23.

Reference Type DERIVED
PMID: 30351999 (View on PubMed)

Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-36. doi: 10.1056/NEJMoa1502309.

Reference Type DERIVED
PMID: 26287849 (View on PubMed)

Other Identifiers

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2011-004426-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO28072

Identifier Type: -

Identifier Source: org_study_id