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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01739764
• Other study ID #: GO28399
• Secondary ID: 2012-003144-80
• Status: Completed
• Phase: Phase 4
• Start date: February 19, 2013
• Est. completion date: February 17, 2020

Study information

• Verified date: December 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: February 17, 2020
• Est. primary completion date: February 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Vemurafenib
Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).

Locations

Country	Name	City	State
Belarus	N.N. Alexandrov National Cancer Centre of Belarus	Minsk District
Belgium	Institut Jules Bordet	Brussels
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	University Clinic Centre Sarajevo	Sarajevo
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Croatia	Clinical Hospital Center Sestre Milosrdnice	Zagreb
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Cyprus	Bank of Cyprus Oncology Center	Nicosia
Egypt	Medical Research Institute	Alexandria
Egypt	National Cancer Institute	Cairo
Egypt	Mansoura University Hospital	Dakahlia
Egypt	Gharbia Cancer Society	Tanta
France	Centre Léon Bérard	Lyon
France	Institut Gustave Roussy	Villejuif
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Apotheke	Mainz
Germany	Universitätsklinikum Wurzburg	Würzburg
Greece	University General Hospital of Heraklion	Crete
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Központ; Borgyógyászati Klinika	Debrecen
Hungary	Pecsi Tudomanyegyetem	Pecs
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)	Milano	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Maastricht University Medical Center	Maastricht
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Clinical Studies Trust	Christchurch
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Medisprof SRL	Cluj-Napoca
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan
Russian Federation	SBIH " Clinical Oncological Dispensary # 1"; Chemotherapy department #1 and #2	Krasnodar
Russian Federation	Moscow city oncology hospital #62 of Moscow Healthcare Department	Moscow
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement	Moskva	Moskovskaja Oblast
Russian Federation	St. Petersburg SHI "City Clinical Oncology Dispensary"	Saint-Petersburg
Russian Federation	SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan	Ufa
Serbia	Clinical Center Bezanijska Kosa	Belgrade
Serbia	Institute for Oncology and Radiology of Serbia; Medical Oncology	Belgrade
South Africa	Cape Town Oncology Trials	Cape Town
South Africa	Wits Donald Gordon Clinical Trial Centre; Medical Oncology	Parktown, Johannesburg
South Africa	Cancercare Langenhoven Drive Oncology Centre	Port Elizabeth
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	LA Coruña
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Santa Lucia	Cartagena (Murcia)	Murcia
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid
Spain	Hospital Regional Universitario de Malaga; Oncologia	Málaga	Malaga
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Marsden Hospital	Surrey
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Chicago Medical Center; Medicine, Section of Pulmonary	Chicago	Illinois
United States	Mary Crowley Medical Research Center; Oncology	Dallas	Texas
United States	UCLA Department of Medicine	Los Angeles	California
United States	Evelyn H. Lauder Center	New York	New York
United States	New York University Medical Center PRIME	New York	New York
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Highlands Oncology Group	Rogers	Arkansas
United States	University of Washington Seattle Cancer Care Alliance	Seattle	Washington
United States	Siouxland Regional Cancer Center d/b/a June E. Nylen Cancer Center	Sioux City	Iowa
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California
United States	M D Anderson Physician Network	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Bosnia and Herzegovina,  Brazil,  Canada,  Croatia,  Cyprus,  Egypt,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).