Trial Outcomes & Findings for A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation (NCT NCT01286753)

Last Updated: 2016-09-07

Results Overview

Best overall response rate was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Best overall response rate: the percentage of participants with best objective response of complete response (CR) or partial response (PR) (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 millimeters (mm). PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Up to approximately 4 years

Results posted on

2016-09-07

Participant Flow

Written informed consent for participation in the study was obtained before performing any study-specific screening tests or evaluations.

Participant milestones

Participant milestones
Measure	Tyrosine Kinase Inhibitor (TKI) Naive Vemurafenib 960 milligrams (mg) orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
Overall Study STARTED	26	25
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	26	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Tyrosine Kinase Inhibitor (TKI) Naive Vemurafenib 960 milligrams (mg) orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
Overall Study Adverse Event	7	6
Overall Study Progression	11	13
Overall Study Refused Treatment	1	0
Overall Study Withdrawal of Consent	0	2
Overall Study Discontinued to Join Extension Study	6	4
Overall Study Participant to Receive Radiotherapy	1	0

Baseline Characteristics

A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=25 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.	Total n=51 Participants Total of all reporting groups
Age, Continuous	62.9 years STANDARD_DEVIATION 13.5 • n=5 Participants	65.2 years STANDARD_DEVIATION 9.1 • n=7 Participants	64.0 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 4 years

Population: Efficacy population (TKI Naive group only), defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Best Overall Response Rate in TKI-Naive Participants	42.3 percentage of participants Interval 23.35 to 63.08	—

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Efficacy population (TKI Experienced group only), defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Best overall response rate was assessed by the investigators according to RECIST v1.1. Best overall response rate: the percentage of participants with best objective response of CR or PR (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.

Outcome measures

Outcome measures
Measure	TKI Naive n=22 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Best Overall Response Rate in TKI-Experienced Participants	27.3 percentage of participants Interval 10.73 to 50.22	—

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Efficacy population, defined as all enrolled participants who received at least one dose of study treatment and excluding 3 participants in the TKI Experienced group who had previous BRAFi or MEKi treatment or withdrew consent.

Clinical benefit rate: the percentage of participants with confirmed CR, PR, or stable disease (SD; maintained for at least 6 months) as assessed by investigators according to RECIST v1.1. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, compared to the baseline sum diameters.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=22 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Clinical Benefit Rate	73.1 percentage of participants Interval 52.21 to 88.43	54.5 percentage of participants Interval 32.21 to 75.61

SECONDARY outcome

Timeframe: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)

Duration of response (for participants with confirmed best response CR or PR): the interval between earliest qualifying response and date of progression of disease (PD) or death for any cause, whichever occurred first; participants with no documented progression after CR or PR were censored at the date of last known CR or PR, respectively. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=22 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Duration of Response	9.5 months Interval 5.7 to NA = Not estimable due to an insufficient number of events.	7.4 months Interval 3.7 to NA = Not estimable due to an insufficient number of events.

SECONDARY outcome

Timeframe: From the day of first treatment until the first documented PD or death (up to approximately 4 years)

Progression-free survival: the interval between the day of first treatment and the first documentation of PD or death; participants who were withdrawn from the study without documented progression were censored at the date of the last tumor assessment when the participant was known to be progression-free; participants without post baseline tumor assessments were censored at the time of enrollment. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=22 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Progression-Free Survival	18.2 months Interval 15.5 to 29.3	8.9 months Interval 5.5 to 27.7

SECONDARY outcome

Timeframe: From the date of first treatment to the date of death for any cause (up to approximately 4 years)

Population: Intent-to-Treat population, defined as all enrolled participants.

Overall survival: the interval between the date of first treatment to the date of death, regardless of the cause of death; participants who were alive at the time of the analysis were censored at the date of the last known alive; participants with no post baseline information were censored at the time of enrollment.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=25 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Overall Survival	NA months Interval 28.3 to NA = Not estimable due to an insufficient number of events.	14.4 months Interval 8.2 to 29.1

SECONDARY outcome

Timeframe: Baseline until 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 4 years)

Population: Safety population, defined as enrolled participants who received at least one dose of study treatment.

An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Outcome measures
Measure	TKI Naive n=26 Participants Vemurafenib 960 mg orally twice daily in participants naive to any prior systemic TKI therapy.	TKI Experienced n=25 Participants Vemurafenib 960 mg orally twice daily in participants previously treated with TKI therapy active against VEGFR.
Percentage of Participants With Adverse Events	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Data were not collected for this outcome.

AUC is a measure of the drug or biologic concentration in the body following administration.

Outcome measures

Outcome data not reported

Adverse Events

TKI Naive

Serious events: 16 serious events

Other events: 26 other events

Deaths: 0 deaths

TKI Experienced

Serious events: 18 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER