An open-label, multicenter study to assess the safety of RO5185426 in patients with metastatic melanoma

• Register: EUCTR
• Last refreshed on: 20 February 2017
• Main ID: EUCTR2010-023526-21-IE
• Date of registration: 06/10/2011
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: An open-label, multicenter study to assess the safety of RO5185426 in patients with metastatic melanoma
• Scientific title: An open-label, multicenter study to assess the safety of RO5185426 in patients with metastatic melanoma
• Date of first enrolment: 20/12/2011
• Target sample size: 3300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023526-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Estonia, Finland, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Macedonia, the former Yugoslav Republic of, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom

Contacts

• Name: Trial Information Support Line TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female patients =16 years of age
- Patients with histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) with documented BRAF V600 mutation determined by the cobas® 4800 BRAF V600 Mutation Test prior to
administration of RO5185426. Unresectable stage IIIC disease must have confirmation from a surgical oncologist
- Patients with either measurable or non-measurable disease (RECIST Version 1.1)
- Patients may or may not have received prior systemic therapy for metastatic melanoma
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
- Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
- Adequate hematologic, renal and liver function as defined by the following laboratory values performed within 7 days prior to first dose of RO5185426:
Absolute neutrophil count (ANC) = 1.5 x 109/L
Platelet count = 100 x 109/L
Hemoglobin = 9 g/dL
Serum creatinine = 1.5 times upper limit of normal (ULN) or creatine clearance (CrCl) > 50 mL/hr by Cockroft–Gault formula
Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) = 2.5 times ULN (= 5 times ULN if considered due to tumour)
Serum bilirubin = 1.5 times ULN
Alkaline phosphatase = 2.5 times ULN (= 5 times ULN if considered due to tumour)
- Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal 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. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance.[Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.]
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry
- Signed informed consent must be obtained prior to performing any study-related procedures (including tumour testing for the V600 BRAF mutation)
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2381
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 914

Exclusion criteria:
- Evidence of symptomatic CNS lesions as determined by investigator, use of steroids or anti-seizure medications for the treatment of brain metastases prior to the first administration of RO5185426. Patients with asymptomatic lesions previously irradiated or surgically resected that are radiologically stable are eligible. Patients with incidentally found brain metastasis that are asymptomatic and for which no treatment is planned are also eligible
- Patients with a previous malignancy (other than melanoma) within the past 2 years are excluded except patients with treated and controlled basal or squamous cell carcinoma (SCC) of the skin or carcinoma in-situ of the cervix. Isolated
elevation in prostate-specific antigen in absence of
radiographic evidence of metastatic prostate cancer is allowed
- Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study
- Known hypersensitivity to RO5185426 or another BRAF inhibitor
- Pregnant or lactating women
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets
- Any of the following within the 6 months prior to first RO5185426 administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications
- History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias = Grade 2 (NCI CTCAE Version 4.0)
- Corrected QT (QTc) interval = 450 msec at baseline
- Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics)
- Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or RO5185426 administration, or may interfere with the interpretation of study results, which in the judgment of the investigator would
make the patient inappropriate for entry into this study
- Unwillingness to practice effective birth control
- Inability to comply with other requirements of the protocol


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

Health Condition(s) or Problem(s) studied

Patients with histologically confirmed metastatic melanoma harbouring the BRAF V600 mutation as determined by the cobas® 4800 BRAF V600 Mutation Test.
MedDRA version: 17.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Zelboraf 240 mg Film-coated Tablets
Product Name: RO5185426
Product Code: RO5185426/F17
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: vemurafenib
CAS Number: 918504-65-1
Current Sponsor code: RO5185426-006
Other descriptive name: RG7204, PLX4032
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Primary Outcome(s)

Primary end point(s): The primary objective of this clinical trial is to evaluate the safety and tolerability of RO5185426 in patients with metastatic melanoma (surgically incurable and unresectable stage IIIC or Stage IV, AJCC) harbouring the BRAF V600 mutation (identified by the cobas® 4800 BRAF V600 Mutation Test). Hence the following safety variables are primary variables: adverse events (all AEs, AEs grade 3 or 4, AEs of special interest, AEs leading to drug interruptions or discontinuations, serious adverse events (SAEs), dermatological evaluations and other assessments for SCC (chest CT scan, anal examination, cervical examination and head/neck examination), assessment for second primary malignancies, premature discontinuation from study and treatment, laboratory parameters and study medication.

Main Objective: To evaluate the safety and tolerability of RO5185426 in patients with metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) harbouring the BRAF V600 mutation

Secondary Objective: To evaluate the efficacy of RO5185426 as objective response rates (ORRs) determined by the investigator (RECIST, Version 1.1)

Timepoint(s) of evaluation of this end point: 46 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 46 months

Secondary end point(s): To evaluate the efficacy of RO5185426 as overall
response rates (ORRs) determined by the investigator (RECIST, Version 1.1) as allowed by local regulatory requirements. Additional efficacy parameters will be calculated including time to tumour response, duration of response, progression free survival (PFS) and overall survival (OS)

Secondary ID(s)

NCT01307397

2010-023526-21-ES

MO25515

Source(s) of Monetary Support

F.Hoffmann-La Roche Ltd.