Clinical trial NCT01524978: A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers
Official title: An Open-label, Phase II Study of Vemurafenib in Patients With BRAF V600 Mutation-positive Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma, Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-02-02
Enrollment: 208
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Confirmed Best Overall Response Rate (BORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Percentage of Participants With Confirmed Clinical Benefit
timeFrame: Up to approximately 3 years
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Time to Response
timeFrame: Up to approximately 3 years
measure: Time to Tumor Progression (TTP)
timeFrame: Up to approximately 3 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab
timeFrame: Up to approximately 3 years
measure: Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab
timeFrame: Up to 28 days
measure: Safety: Percentage of Participants With Adverse Event
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital;Oncology
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Bordeaux
country: France
facility: Institut Bergonie; Oncologie
city: Caen
country: France
facility: Centre Francois Baclesse; Oncologie
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Marseille Cedex 09
country: France
facility: Institut Paoli-Calmettes; Oncologie Medicale 1
city: Saint Herblain
country: France
facility: Centre Rene Gauducheau
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave Roussy; Sitep
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
city: Köln
country: Germany
facility: Klinik der Uni zu Koeln; Klinik I für Innere Medizin; Onkologie
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias; Servicio de Oncologia
state: Asturias
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: London
country: United Kingdom
facility: The Royal Marsden Hospital; Dept of Medicine
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.