A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers

Roche

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma, Neoplasms

Treatments: Drug: vemurafenib; Drug: cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01524978

MO28072

2011-004426-10 (EudraCT Number)

Details and patient eligibility

About

This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.

Enrollment: 208 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Must have recovered from all side effects of their most recent systemic or local treatment
• Adequate hematological, renal and liver function

For solid tumors only:

• Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
• Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)

For multiple myeloma only:

• Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
• Must have received at least one prior systemic therapy for the treatment of multiple myeloma
• Treated with local radiotherapy
• Must have relapsed and/or refractory multiple myeloma with measurable disease

Exclusion criteria

• Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
• Uncontrolled concurrent malignancy
• Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
• Active or untreated central nervous system (CNS) metastases
• History of or known carcinomatous meningitis
• Concurrent administration of any anti-cancer therapies other than those administered in this study
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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208 participants in 7 patient groups

Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib

Experimental group

Description:

Participants with NSCLC will be treated with vemurafenib monotherapy.

Treatment:

Drug: vemurafenib

Drug: vemurafenib

Cohort 2: Ovarian Cancer - vemurafenib

Experimental group

Description:

Participants with ovarian cancer will be treated with vemurafenib monotherapy.

Treatment:

Drug: vemurafenib

Drug: vemurafenib

Cohort 3a: Colorectal Cancer - vemurafenib

Experimental group

Description:

Participants with colorectal cancer will be treated with vemurafenib monotherapy.

Treatment:

Drug: vemurafenib

Drug: vemurafenib

Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab

Experimental group

Description:

Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy.

Treatment:

Drug: vemurafenib

Drug: cetuximab

Drug: vemurafenib

Cohort 4: Cholangiocarcinoma - vemurafenib

Experimental group

Description:

Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy.

Treatment:

Drug: vemurafenib

Drug: vemurafenib

Cohort 6: Multiple Myeloma - vemurafenib

Experimental group

Description:

Participants with multiple myeloma will be treated with vemurafenib monotherapy.

Treatment:

Drug: vemurafenib

Drug: vemurafenib

Cohort 7: Other Solid Tumors - vemurafenib

Experimental group

Description:

Participants with Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), anaplastic thyroid cancer, advanced stage astrocytoma, early stage astrocytoma and other BRAF V600-positive tumors will be treated with vemurafenib monotherapy. Subcohorts will be analyzed separately if 7 or more participants are enrolled for each indication.

Treatment:

Drug: vemurafenib

Drug: vemurafenib