Patients with cancers (excluding melanoma and papillary thyroid cancer) harboring BRAF V600 mutations as identified by the routinely performed mutation analysis assays at each individual participating site MedDRA version: 18.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cy
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 16 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? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
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. •Patients with incidentally found brain metastases that are asymptomatic and for which no treatment is planned are also eligible. •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.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the safety and tolerability of vemurafenib in patients with cancers harboring BRAF V600 mutations. To evaluate in solid tumors and multiple myeloma (MM) overall response rate (ORR), clinical benefit rate (CR (or sCR), PR (or VGPR)) and stable disease [SD]),of vemurafenib, duration of response (DOR), time to response, time to tumor progression (TTP), PFS, and overall survival (OS).; Timepoint(s) of evaluation of this end point: Incidence of adverse events. Overall Response Rate / Tumor assessments according to RECIST Criteria 1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of vemurafenib in patients with cancers harboring BRAF V600 mutations as response rate (RR) at Week 8 determined by the Investigator using Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria and to identify tumor types for further development ; Secondary Objective: · To evaluate the safety and tolerability of vemurafenib in this patient population. · To evaluate in solid tumors and multiple myeloma overall response rate, clinical benefit rate,Clinical response or Stringent Complete Response, partial response or very good partial response and stable disease of vemurafenib, duration of response, time to response, time to tumor progression, progression free survival and overall survival. · To determine the max tolerated dose and recommended dose for stage I/II of the combination of vemurafenib and cetuximab in BRAF V600-positive metastatic CRC patients (Cohort 3b only). · To investigate the safety, tolerability, efficacy of the combination of vemurafenib and cetuximab in BRAF V600-positive metastatic CRC patients (Cohort 3b only). · To evaluate tumour assessment scans by an IRC for Cohort 1 (NSCLC) and other cohorts that demonstrate clinically meaningful efficacy per investigator assessment. ;Primary end point(s): To evaluate the efficacy of vemurafenib in patients with cancers harboring BRAF V600 mutations as response rate (RR) at Week 8 determined by the Investigator using Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria and to identify tumor types for further development ;Timepoint(s) of evaluation of this end point: Week 8 of vemurafenib treatment | — |
Countries
China, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed