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

NCT01524978 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MO280722011-004426-10
• Study Type: interventional
• Target: 208
• Locations: 6 countries
• Sites: 34

Brief Summary

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.

Conditions

Multiple Myeloma, Neoplasms

Outcome Measures

Primary Outcomes (1)

• Confirmed Best Overall Response Rate (BORR)

  Confirmed BORR: percentage of participants with an objective response (OR) (complete response \[CR\], partial response \[PR\], stringent CR \[sCR\] or very good PR \[VGPR\]) on 2 occasions \>/= 4 weeks apart as assessed by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or International Myeloma Working Group (IMWG) criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: \>/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \</= 5% plasma cells in bone marrow; PR: \>/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>/= 90% or to \<200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hour; sCR: CR plus normal free light chain (FLC) ratio and no clonal cells in bone marrow.

  Up to approximately 3 years

Secondary Outcomes (10)

• Percentage of Participants With Confirmed Clinical Benefit

  Up to approximately 3 years

• Overall Response Rate (ORR)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Time to Response

  Up to approximately 3 years

• Time to Tumor Progression (TTP)

  Up to approximately 3 years

Study Arms (7)

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

EXPERIMENTAL

Participants with NSCLC will be treated with vemurafenib monotherapy.

Drug: vemurafenib

Cohort 2: Ovarian Cancer - vemurafenib

EXPERIMENTAL

Participants with ovarian cancer will be treated with vemurafenib monotherapy.

Drug: vemurafenib

Cohort 3a: Colorectal Cancer - vemurafenib

EXPERIMENTAL

Participants with colorectal cancer will be treated with vemurafenib monotherapy.

Drug: vemurafenib

Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab

EXPERIMENTAL

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

Drug: cetuximab; Drug: vemurafenib

Cohort 4: Cholangiocarcinoma - vemurafenib

EXPERIMENTAL

Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy.

Drug: vemurafenib

Cohort 6: Multiple Myeloma - vemurafenib

EXPERIMENTAL

Participants with multiple myeloma will be treated with vemurafenib monotherapy.

Drug: vemurafenib

Cohort 7: Other Solid Tumors - vemurafenib

EXPERIMENTAL

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.

Drug: vemurafenib

Interventions

cetuximab DRUG

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

Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab

vemurafenib DRUG

Escalating doses given orally twice a day starting on Day 2

Also known as: Zelboraf

Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (34)

Arizona Oncology

Tucson, Arizona, 85704, United States

Location

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, 80012, United States

Location

Massachusetts General Hospital;Oncology

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, 98902, United States

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Institut Bergonie; Oncologie

Bordeaux, 33076, France

Location

Centre Francois Baclesse; Oncologie

Caen, 14076, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut Paoli-Calmettes; Oncologie Medicale 1

Marseille, 13273, France

Location

Centre Rene Gauducheau

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy; Sitep

Villejuif, 94805, France

Location

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

Cologne, 50937, Germany

Location

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

Essen, 45122, Germany

Location

Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum

Mannheim, 68167, Germany

Location

Hospital Univ. Central de Asturias; Servicio de Oncologia

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Fundacion Jimenez Diaz; Servicio de Oncologia

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

Salamanca, 37007, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

The Royal Marsden Hospital; Dept of Medicine

London, SW3 5PT, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37934000 DERIVED

• 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.

  PMID: 30351999 DERIVED

• 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.

  PMID: 26287849 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

Cetuximab; Vemurafenib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2012
• First Posted: February 2, 2012
• Study Start: April 12, 2012
• Primary Completion: October 28, 2016
• Study Completion: October 28, 2016
• Last Updated: November 20, 2017
• Results First Posted: November 20, 2017

Record last verified: 2017-10

Locations

GB (3); US (11); DE (3); CN (1); FR (8); ES (8)