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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01286753
• Other study ID #: NO25530
• Secondary ID: 2010-024133-23
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 28, 2011
• Last updated: November 24, 2014
• Start date: June 2011
• Est. completion date: October 2015

Study information

• Verified date: November 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This open-label, multi-center study will evaluate the safety and efficacy of RO5 185426 in patients with metastatic or unresectable papillary thyroid cancer posi tive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Pat ients will receive RO5185426 960 mg orally twice daily until progressive disease or unacceptable toxicity occurs.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: October 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients. >/= 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; patients 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) or including (Cohort 2) tyrosine kinase inhibitor (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 thyroid carcinoma (PTC), including squamous cell variants of PTC or PTC with areas of squamous metaplasia

• Active or untreated CNS 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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Neoplasms
• Thyroid Neoplasms

Intervention

Drug:
• RO5185426
960 mg orally twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best overall response rate (BORR) in tyrosine kinase inhibitor (TKI)-naïve patients (Cohort 1), assessed by the investigator according to RECIST criteria		18 months	No
Secondary	Clinical benefit rate (objective response rate + stable disease) in TKI-naïve patients		18 months	No
Secondary	Duration of response in TKI-naïve patients		4.5 years	No
Secondary	Progression-free survival in TKI-naïve patients		4.5 years	No
Secondary	Overall survival in TKI-naïve patients		4.5 years	No
Secondary	Best overall response rate in TKI-exposed patients (Cohort 2)		18 months	No
Secondary	Clinical benefit rate in TKI-exposed patients		18 months	No
Secondary	Duration of response in TKI-exposed patients		4.5 years	No
Secondary	Progression-free survival in TKI-exposed patients		4.5 years	No
Secondary	Overall survival in TKI-exposed patients		4.5 years	No
Secondary	Safety: Incidence of adverse events		4.5 years	No
Secondary	Pharmacokinetics: Area under the concentration-time curve (AUC)		up to 4.5 years	No