Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01286753
First received: January 28, 2011
Last updated: July 22, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Neoplasms
Drug: Vemurafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Best Overall Response Rate in TKI-Naive Participants [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the day of first treatment until the first documented PD or death (up to approximately 4 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the date of first treatment to the date of death for any cause (up to approximately 4 years) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to approximately 4 years ] [ Designated as safety issue: No ]
    AUC is a measure of the drug or biologic concentration in the body following administration.


Enrollment: 51
Study Start Date: June 2011
Study Completion Date: May 2015
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tyrosine Kinase Inhibitor (TKI) Naive
Vemurafenib in participants naive to any prior systemic TKI therapy.
Drug: Vemurafenib
Vemurafenib 960 mg orally twice daily.
Other Names:
  • Zelboraf®
  • RO5185426
Experimental: TKI Experienced
Vemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
Drug: Vemurafenib
Vemurafenib 960 mg orally twice daily.
Other Names:
  • Zelboraf®
  • RO5185426

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286753

Locations
United States, California
Torrance, California, United States, 90502
United States, Connecticut
New Haven, Connecticut, United States, 06510
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, New York
New York, New York, United States, 10017
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Houston, Texas, United States, 77030
France
Lyon, France, 69008
Paris, France, 75651
Villejuif, France, 94805
Italy
Milano, Lombardia, Italy, 20133
Pisa, Toscana, Italy, 56124
Netherlands
Groningen, Netherlands, 9700 RB
Leiden, Netherlands, 2300 RC
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01286753     History of Changes
Other Study ID Numbers: NO25530  2010-024133-23 
Study First Received: January 28, 2011
Results First Received: July 22, 2016
Last Updated: July 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Neoplasms
Carcinoma
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on December 08, 2016