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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Vemurafenib

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69008
  • Paris, France, 75651
  • Villejuif, France, 94805
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20133
  • Toscana
    • Pisa, Toscana, Italy, 56124
• Netherlands
  • Groningen, Netherlands, 9700 RB
  • Leiden, Netherlands, 2300 RC
• United States
  • California
    • Torrance, California, United States, 90502
  • Connecticut
    • New Haven, Connecticut, United States, 06510
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Maryland
    • Baltimore, Maryland, United States, 21231
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114
  • New York
    • New York, New York, United States, 10017
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: RO5185426; Zelboraf®
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: RO5185426; Zelboraf®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 4 years
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.	Up to approximately 4 years
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.	From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)
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.	From the day of first treatment until the first documented PD or death (up to approximately 4 years)
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.	From the date of first treatment to the date of death for any cause (up to approximately 4 years)
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.	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)
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.	Up to approximately 4 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: January 28, 2011
• First Submitted That Met QC Criteria: January 28, 2011
• First Posted (Estimate): January 31, 2011

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: July 22, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Thyroid Neoplasms; Thyroid Cancer, Papillary; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: NO25530; 2010-024133-23