BRIM 3: A Randomized, Open-label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma with V600E BRAF Mutation Receiving RO5185426 or Dacarbazine. - BRIM 3

• Register: EUCTR
• Last refreshed on: 21 August 2012
• Main ID: EUCTR2009-012293-12-FR
• Date of registration: 19/11/2009
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: BRIM 3: A Randomized, Open-label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma with V600E BRAF Mutation Receiving RO5185426 or Dacarbazine. - BRIM 3
• Scientific title: BRIM 3: A Randomized, Open-label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma with V600E BRAF Mutation Receiving RO5185426 or Dacarbazine. - BRIM 3
• Date of first enrolment: 11/01/2010
• Target sample size: 680
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012293-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

France, Germany, Italy, Netherlands, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
. Male or female patients = 18 years of age
. Patients with histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV, AJCC). Unresectable stage IIIC disease must have confirmation from a surgical oncologist
. Treatment naïve patients (i.e., NO prior systemic anticancer therapy for advanced disease; Stage IIIC and IV). Only prior adjuvant immunotherapy is allowed
. Patients must have a positive BRAF V600E mutation result determined by a designated laboratory using a Roche CoDx BRAF mutation test prior to administration of RO5185426
. Measurable disease (by RECIST criteria version 1.1) prior to the administration of RO5185426
. Negative serum pregnancy test within 10 days prior to commencement of dosing in pre-menopausal women. Women of non-childbearing potential may be included if
they are either surgically sterile or have been postmenopausal for = 1 year
. Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician (in accordance with local requirements)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
. Patients with active CNS lesions are excluded
. History of carcinomatous meningitis
. Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic attack, or symptomatic pulmonary embolism
. Patients with a previous malignancy within the past 5 years are excluded except for patients with basal or squamous cell carcinoma (SCC) of the skin, melanoma in-situ, and carcinoma in-situ of the cervix. Isolated elevation in PSA in the absence of radiographic evidence of metastatic prostate cancer is allowed


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

First-line therapy for adult patients with histologically confirmed metastatic melanoma (unresectable Stage IIIC or Stage IV) harbouring the V600E positive mutation
MedDRA version: 12.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma

Intervention(s)

Product Code: RO5185426/F17
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO5185426-006
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Trade Name: Dacarbazine Pliva
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Dacarbazine
CAS Number: 4342-03-4
Other descriptive name: DTIC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Dacarbazine
CAS Number: 4342-03-4
Other descriptive name: DTIC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Secondary Objective: • To further assess efficacy of RO5185426 compared to dacarbazine based on progression-free survival (PFS), best overall response rate (BORR), time to response, duration of response, and time to treatment failure
• To evaluate the tolerability and safety profile of RO5185426 using the NCI CTCAE (version 4.0)
• To further characterize the pharmacokinetic (PK) profile of RO5185426
• To contribute to the validation of the Roche Companion Diagnostic (CoDx) cobas® 4800 BRAF V600E test for the detection of BRAF mutations in DNA extracted from formalin-fixed paraffin embedded tumour (FFPET) samples

Primary end point(s): The primary efficacy endpoint is overall survival, which is defined as the interval (days) between randomization and death for any cause. For a patient alive at the time of analysis data cutoff, OS time will be censored at the last date the patient was known to be alive.

Main Objective: To evaluate efficacy of RO5185426 as a monotherapy compared to dacarbazine in terms of overall survival (OS) in previously untreated patients with advanced melanoma harbouring the BRAF V600E mutation

Secondary ID(s)

NO25026

2009-012293-12-NL