Clinical trial NCT01286753: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Best Overall Response Rate in TKI-Naive Participants
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Best Overall Response Rate in TKI-Experienced Participants
timeFrame: Up to approximately 4 years
measure: Clinical Benefit Rate
timeFrame: Up to approximately 4 years
measure: Duration of Response
timeFrame: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)
measure: Progression-Free Survival
timeFrame: From the day of first treatment until the first documented PD or death (up to approximately 4 years)
measure: Overall Survival
timeFrame: From the date of first treatment to the date of death for any cause (up to approximately 4 years)
measure: Percentage of Participants With Adverse Events
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)
measure: Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: Torrance
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Lyon
country: France
city: Paris
country: France
city: Villejuif
country: France
city: Milano
country: Italy
state: Lombardia
city: Pisa
country: Italy
state: Toscana
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.