Neoplasms
Conditions
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.
Interventions
DRUGVemurafenib
Vemurafenib was given based on the last dose of the antecedent study (minimum 480 mg orally BID).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
Belarus, Belgium, Bosnia and Herzegovina, Brazil, Canada, Croatia, Cyprus, Egypt, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, New Zealand, Portugal, Romania, Russia, Serbia, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 82 centers in 24 countries.
Pre-assignment details
215 participants were enrolled into this OLE study and were included in the Safety population.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 29 |
| 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. | 40 |
| 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. | 146 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 4 |
| Overall Study | Death | 4 | 6 | 38 |
| Overall Study | Lost to Follow-up | 0 | 0 | 5 |
| Overall Study | Multiple Reasons | 3 | 2 | 3 |
| Overall Study | Non-Compliance | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 2 | 4 |
| Overall Study | Progressive Disease | 3 | 5 | 16 |
| Overall Study | Protocol Violation | 0 | 0 | 2 |
| Overall Study | Study Terminated by Sponsor | 8 | 13 | 26 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 27 |
Baseline characteristics
| Characteristic | Vemurafenib 720mg BID | Vemurafenib 960mg BID | Vemurafenib 480mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 60.6 Years STANDARD_DEVIATION 12.4 | 52.3 Years STANDARD_DEVIATION 13.5 | 60.4 Years STANDARD_DEVIATION 11.7 | 54.9 Years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Asian | 2 Participants | 39 Participants | 2 Participants | 43 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 37 Participants | 137 Participants | 24 Participants | 198 Participants |
| Race/Ethnicity, Customized Not Stated | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 4 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 101 Participants | 23 Participants | 161 Participants |
| Sex: Female, Male Female | 20 Participants | 57 Participants | 18 Participants | 95 Participants |
| Sex: Female, Male Male | 20 Participants | 89 Participants | 11 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 29 | 6 / 40 | 38 / 146 |
| other Total, other adverse events | 21 / 29 | 29 / 40 | 119 / 146 |
| serious Total, serious adverse events | 14 / 29 | 15 / 40 | 29 / 146 |
Outcome results
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.
Time frame: Baseline up to a maximum of 7 years.
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication. Please note that for this Outcome Measure, one participant who received 960 mg BID of Vemurafenib had no treatment end date indicated and was excluded from the calculation of study treatment exposure summaries.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib 480mg BID | Dose Intensity of Vemurafenib | 95.3 Percentage of Planned Dose | Standard Deviation 8.1 |
| Vemurafenib 720mg BID | Dose Intensity of Vemurafenib | 92.9 Percentage of Planned Dose | Standard Deviation 12.1 |
| Vemurafenib 960mg BID | Dose Intensity of Vemurafenib | 94.5 Percentage of Planned Dose | Standard Deviation 11 |
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).
Time frame: Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vemurafenib 480mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 93.1 Percentage of Participants |
| Vemurafenib 480mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 48.3 Percentage of Participants |
| Vemurafenib 720mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 92.5 Percentage of Participants |
| Vemurafenib 720mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 37.5 Percentage of Participants |
| Vemurafenib 960mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 93.2 Percentage of Participants |
| Vemurafenib 960mg BID | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 19.9 Percentage of Participants |