An open-label, phase II study of vemurafenib in patients with BRAF V600 mutation-positive cancers

Phase 1

• Conditions: Patients with cancers (excluding melanoma and papillary thyroidcancer) harboring BRAF V600 mutations as identified by theroutinely performed mutation analysis assays at each individualparticipating site; MedDRA version: 14.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-004426-10-ES
• Lead Sponsor: F. Hoffman-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-19
• Last Update Posted: 9 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 121

Inclusion Criteria

For solid tumor cancer patients only:
?Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) that harbor a BRAF V600 mutation and are refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator
?Measurable disease according to RECIST, v1.1

For multiple myeloma (MM) patients only:
?Patients with a confirmed diagnosis of MM and harbor a BRAF V600 mutation
?Patients must have received at least one line of prior systemic therapy for the treatment of MM. A line of treatment is sequential treatment without interruption for response and subsequent progression
?Patients treated with local radiotherapy (with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression), two weeks must have lapsed since the last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry into the Study deferred until the radiotherapy is completed and two weeks have passed since the last date of therapy
?Patients must have relapsed and/or refractory MM with measurable disease, defined as disease that can be measured either by serum or urinary evaluation of the monoclonal component or by serum assay of free light chain (FLC) based on at least one of the following three measurements:
oSerum M-protein > 0.5 g/dL
oUrine M-protein > 200 mg per 24 hours
oInvolved FLC level > 10 mg/dL (> 100 mg/L) provided serum FLC ratio is abnormal

For all patients (solid tumors and MM patients):
?Male or female ? 18 years of age
?Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0?2
?Adequate hematologic, renal, and liver function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 61
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

?Melanoma, papillary thyroid cancer, or hematological malignancies (with the exception of multiple myeloma)
?Uncontrolled concurrent malignancy (early stage or chronic disease is allowed if not requiring active therapy or intervention and is under control)
?For MM, solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
?Active or untreated CNS metastases. Patients with brain metastasis are eligible if asymptomatic, off corticosteroid therapy and without evidence of disease progression in brain for ? 2 months.
?Concurrent administration of any anti-cancer therapies (e.g., chemotherapy, other targeted therapy, experimental drug, etc.) other than those administered in this study
?Prior treatment with a BRAF or MEK inhibitor (prior sorafenib is allowed)
?Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified