An Extension (Rollover) Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol

An Open-Label, Extension (Rollover) Study of Vemurafenib in Patients With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol

This open-label, multicenter, non-randomized study provided continued access to vemurafenib for eligible participants with BRAF V600 mutation-positive malignancy, who were previously enrolled and treated in an antecedent vemurafenib protocol and did not meet the protocol's criteria for disease progression, or were treated beyond progression and were still deriving clinical benefit (as assessed by investigator), and may have therefore potentially benefited from continued treatment with vemurafenib. Participants received treatment with oral vemurafenib at 960 milligrams (mg) twice daily (BID), 720 mg BID, or 480 mg BID, depending on the last dose in the antecedent protocol. Treatment continued until progression of disease or as long as the participant was deriving clinical benefit, as judged by the investigator (case-by-case decision with approval of the Medical Monitor), death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the Sponsor to terminate the study, whichever occurred first.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Vemurafenib

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belarus
  • Minsk District, Belarus, 223040
    • N.N. Alexandrov National Cancer Centre of Belarus
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Center of The Republic Of Srpska
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinic Centre Sarajevo
• Brazil
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital das Clinicas - UFRGS
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Center Sestre Milosrdnice
• Cyprus
  • Nicosia, Cyprus, 2006
    • Bank of Cyprus Oncology Center
• Egypt
  • Alexandria, Egypt, 21131
    • Medical Research Institute
  • Cairo, Egypt, 11796
    • National Cancer Institute
  • Dakahlia, Egypt, 324
    • Mansoura University Hospital
  • Tanta, Egypt
    • Gharbia Cancer Society
• France
  • Lyon, France, 69373
    • Centre Leon Berard
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Apotheke
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg
• Greece
  • Crete, Greece, 711 10
    • University General Hospital of Heraklion
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, H-1077
    • Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
  • Debrecen, Hungary, 4012
    • Debreceni Egyetem Klinikai Központ; Bőrgyógyászati Klinika
  • Pecs, Hungary, 7624
    • Pécsi Tudományegyetem
• Israel
  • Haifa, Israel, 3109600
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Ramat Gan, Israel, 5266202
    • Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Lombardia
    • Milano, Lombardia, Italy
      • Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
  • Toscana
    • Pisa, Toscana, Italy, 56100
      • Azienda Ospedaliero Universitaria Pisana
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, (0)6351
    • Samsung Medical Center
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust
• Portugal
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa; Servico de Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Romania
  • Cluj-Napoca, Romania, 400058
    • Medisprof SRL
• Russian Federation
  • Kazan, Russian Federation, 420029
    • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
  • Krasnodar, Russian Federation, 350040
    • SBIH " Clinical Oncological Dispensary # 1"; Chemotherapy department #1 and #2
  • Moscow, Russian Federation, 143423
    • Moscow city oncology hospital #62 of Moscow Healthcare Department
  • Saint-Petersburg, Russian Federation, 197022
    • St. Petersburg SHI "City Clinical Oncology Dispensary"
  • Ufa, Russian Federation, 450054
    • SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
  • Moskovskaja Oblast
    • Moskva, Moskovskaja Oblast, Russian Federation, 115478
      • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement
• Serbia
  • Belgrade, Serbia, 11070
    • Clinical Center Bezanijska kosa
  • Belgrade, Serbia, 11000
    • Institute for Oncology and Radiology of Serbia; Medical Oncology
• South Africa
  • Cape Town, South Africa, 7570
    • Cape Town Oncology Trials
  • Parktown, Johannesburg, South Africa, 2193
    • Wits Donald Gordon Clinical Trial Centre; Medical Oncology
  • Port Elizabeth, South Africa, 6045
    • Cancercare Langenhoven Drive Oncology Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 280146
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46009
    • Instituto Valenciano Oncologia; Oncologia Medica
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07010
      • Hospital Universitario Son Espases
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruna
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Hospital Regional Universitario de Malaga; Oncologia
  • Murcia
    • Cartagena (Murcia), Murcia, Spain, 30202
      • Hospital General Universitario Santa Lucía
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Surrey, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Department of Medicine
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center; Medicine, Section of Pulmonary
  • Iowa
    • Sioux City, Iowa, United States, 51108
      • Siouxland Regional Cancer Center d/b/a June E. Nylen Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center PRIME
    • New York, New York, United States, 10065
      • Evelyn H. Lauder Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • Texas
    • Dallas, Texas, United States, 75246
      • Mary Crowley Medical Research Center; Oncology
    • Webster, Texas, United States, 77598
      • M D Anderson Physician Network
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BRAF V600 mutation-positive malignancy
• Prior eligibility for and on study treatment from an antecedent vemurafenib protocol
• Ability to begin treatment in the extension (rollover) protocol within 15 days following the last day of the study in the antecedent protocol
• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use 2 adequate methods of contraception as defined by protocol during the course of this study and for at least 6 months after completion of study treatment

Exclusion Criteria:

• Adverse event requiring discontinuation of vemurafenib in the antecedent protocol
• Progressive disease during the antecedent protocol. If approval to treat beyond progression was already given in the antecedent protocol, the participant may roll over into the current protocol without sponsor approval. Under special circumstances, enrollment into this protocol and dosing beyond progression may be considered and will require approval of the sponsor

Participants meeting any of the following exclusion criterion of the antecedent study at the time the participant is considered for the extension (rollover) study:

• Current, recent (within 28 days prior to Day 1), or planned use of any antitumor therapy outside this study
• Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study
• History of malabsorption or other clinically significant metabolic dysfunction
• History of clinically significant cardiac or pulmonary dysfunction as specified in antecedent study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vemurafenib 480mg BID; Participants received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf
EXPERIMENTAL: Vemurafenib 720mg BID; Participants received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf
EXPERIMENTAL: Vemurafenib 960mg BID; Participants received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.	Drug: Vemurafenib; Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).; Other Names: Zelboraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Intensity of Vemurafenib	Dose Intensity was defined as (total actual doses taken/total planned doses) *100, where total planned doses = prescribed doses * planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose.	Baseline up to a maximum of 7 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Reported are the Percentage of Participants with AEs and Serious Adverse Events (SAEs).	Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 19, 2013
• Primary Completion (ACTUAL): February 17, 2020
• Study Completion (ACTUAL): February 17, 2020

Study Registration Dates

• First Submitted: November 26, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (ESTIMATE): December 3, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2021
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: GO28399; 2012-003144-80 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No