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

Phase 4

Completed

• Conditions: Neoplasms
• Interventions: Drug: Vemurafenib

• Registration Number: NCT01739764
• Lead Sponsor: Hoffmann-La Roche

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-11-26
• Study First Submitted QC: 2012-11-29
• Study First Posted: 2012-12-03
• Study Start: 2013-02-19
• Primary Completion: 2020-02-17
• Study Completion: 2020-02-17
• Results First Submitted: 2020-10-26
• Results First Submitted QC: 2020-10-27
• Results First Posted: 2020-11-18
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-11
• Last Update Posted: 2021-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 215

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vemurafenib 480mg BID	Vemurafenib	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.
Vemurafenib 960mg BID	Vemurafenib	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.
Vemurafenib 720mg BID	Vemurafenib	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.

Primary Outcome Measures

Name	Time	Method
Dose Intensity of Vemurafenib	Baseline up to a maximum of 7 years.	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).	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).

Trial Locations

Locations (83)

Highlands Oncology Group; 🇺🇸 Rogers, Arkansas, United States

UCLA Department of Medicine; 🇺🇸 Los Angeles, California, United States

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

University of Chicago Medical Center; Medicine, Section of Pulmonary; 🇺🇸 Chicago, Illinois, United States

Siouxland Regional Cancer Center d/b/a June E. Nylen Cancer Center; 🇺🇸 Sioux City, Iowa, United States

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States

New York University Medical Center PRIME; 🇺🇸 New York, New York, United States

Evelyn H. Lauder Center; 🇺🇸 New York, New York, United States

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States

Mary Crowley Medical Research Center; Oncology; 🇺🇸 Dallas, Texas, United States

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