Back to resultsA Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation
Primary Purpose
Neoplasms
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vemurafenib
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Adult participants. >/= 18 years of age
- Histologically confirmed metastatic or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective; participants whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary
- Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test)
- Radioactive Iodine resistant disease
- Prior therapy excluding (Cohort 1, TKI Naive) or including (Cohort 2, TKI Experienced) TKI
- Clinically relevant disease progression according to RECIST criteria within the prior 14 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematological, renal and liver function
Exclusion Criteria:
- Histological diagnosis other than papillary PTC, including squamous cell variants of PTC or PTC with areas of squamous metaplasia
- Active or untreated central nervous system metastases
- History of or known carcinomatous meningitis
- Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study
- Active squamous cell skin cancer that has not been excised or adequately healed post excision
- Previous treatment with any agent that specifically and selectively targets the MEK or BRAF pathway
- Prior radiotherapy to the only measurable lesion
- Clinically relevant cardio-vascular disease or event within the prior 6 months
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tyrosine Kinase Inhibitor (TKI) Naive
TKI Experienced
Arm Description
Vemurafenib in participants naive to any prior systemic TKI therapy.
Vemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
Outcomes
Primary Outcome Measures
Best Overall Response Rate in TKI-Naive Participants
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.
Secondary Outcome Measures
Best Overall Response Rate in TKI-Experienced Participants
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.
Clinical Benefit Rate
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.
Duration of Response
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.
Progression-Free Survival
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.
Overall Survival
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.
Percentage of Participants With Adverse Events
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.
Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)
AUC is a measure of the drug or biologic concentration in the body following administration.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01286753
Brief Title
A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation
Official Title
An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This open-label, multi-center study will evaluate the safety and efficacy of Vemurafenib (RO5185426) in participants with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until progressive disease or unacceptable toxicity occurs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tyrosine Kinase Inhibitor (TKI) Naive
Arm Type
Experimental
Arm Description
Vemurafenib in participants naive to any prior systemic TKI therapy.
Arm Title
TKI Experienced
Arm Type
Experimental
Arm Description
Vemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Other Intervention Name(s)
Zelboraf®, RO5185426
Intervention Description
Vemurafenib 960 mg orally twice daily.
Primary Outcome Measure Information:
Title
Best Overall Response Rate in TKI-Naive Participants
Description
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.
Time Frame
Up to approximately 4 years
Secondary Outcome Measure Information:
Title
Best Overall Response Rate in TKI-Experienced Participants
Description
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.
Time Frame
Up to approximately 4 years
Title
Clinical Benefit Rate
Description
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.
Time Frame
Up to approximately 4 years
Title
Duration of Response
Description
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.
Time Frame
From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)
Title
Progression-Free Survival
Description
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.
Time Frame
From the day of first treatment until the first documented PD or death (up to approximately 4 years)
Title
Overall Survival
Description
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.
Time Frame
From the date of first treatment to the date of death for any cause (up to approximately 4 years)
Title
Percentage of Participants With Adverse Events
Description
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.
Time Frame
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)
Title
Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)
Description
AUC is a measure of the drug or biologic concentration in the body following administration.
Time Frame
Up to approximately 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants. >/= 18 years of age
Histologically confirmed metastatic or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective; participants whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary
Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test)
Radioactive Iodine resistant disease
Prior therapy excluding (Cohort 1, TKI Naive) or including (Cohort 2, TKI Experienced) TKI
Clinically relevant disease progression according to RECIST criteria within the prior 14 months
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate hematological, renal and liver function
Exclusion Criteria:
Histological diagnosis other than papillary PTC, including squamous cell variants of PTC or PTC with areas of squamous metaplasia
Active or untreated central nervous system metastases
History of or known carcinomatous meningitis
Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study
Active squamous cell skin cancer that has not been excised or adequately healed post excision
Previous treatment with any agent that specifically and selectively targets the MEK or BRAF pathway
Prior radiotherapy to the only measurable lesion
Clinically relevant cardio-vascular disease or event within the prior 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Lyon
ZIP/Postal Code
69008
Country
France
City
Paris
ZIP/Postal Code
75651
Country
France
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
27460442
Citation
Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, Sherman SI, Sherman EJ. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1272-82. doi: 10.1016/S1470-2045(16)30166-8. Epub 2016 Jul 23.
Results Reference
derived
Learn more about this trial
A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation
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