An open-label, multicenter expanded access study of RO5185426 in patients with metastatic melanoma. - ND

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2010-023526-21-IT
• Date of registration: 12/05/2011
• Prospective Registration: No
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: An open-label, multicenter expanded access study of RO5185426 in patients with metastatic melanoma. - ND
• Scientific title: An open-label, multicenter expanded access study of RO5185426 in patients with metastatic melanoma. - ND
• Date of first enrolment: 13/04/2011
• Target sample size: 900
• 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: Placebo: Other:

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Adult patients with histologically confirmed metastatic melanoma harboring the BRAF V600 mutation as determined by the cobas 4800 BRAF V600 Mutation Test. Patients with measurable and/or non-measurable disease (as defined by RECIST 1.1) are eligible for enrollment in this trial. Patients must have failed at least one previous systemic treatment for melanoma Eligibility Criteria Inclusion Criteria: 1. Male or female patients = 18 years of age 2. Patients with histologically confirmed metastatic melanoma (Stage IV; AJCC) with documented BRAF V600 mutation determined by the cobas 4800 BRAF V600 Mutation Test prior to administration of RO5185426 3. Patients with either measurable or non-measurable disease (RECIST Version 1.1) 4. Patients must have progressed during or after at least one prior systemic treatment for metastatic melanoma 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 6. Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma 7. 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 tumor) • Serum bilirubin = 1.5 times ULN • Alkaline phosphatase = 2.5 times ULN (= 5 times ULN if considered due to tumor) 8. 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 9. 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.] 10. 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 11. Signed informed consent must be obtained prior to performing any study-related procedures (including tumor testing for the V600 BRAF mutation).
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:
Exclusion Criteria: 1. Evidence of symptomatic CNS lesions as determined by investigator (patients with radiographically stable, asymptomatic lesions previously irradiated or surgically resected are eligible) 2. 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 3. Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study 4. Pregnant or lactating women 5. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets 6. 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 7. History of or presence of linically significant ventricular or atrial dysrhythmias = Grade 2 (NCI CTCAE Version 4.0) 8. Corrected QT (QTc) interval = 450 msec at baseline 9. Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics) 10. 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 11. Unwillingness to practice effective birth control 12. 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

Adult patients with histologically confirmed metastatic melanoma harboring the BRAF V600 mutation as determined by the cobas 4800 BRAF V600 Mutation Test. Patients must have failed at least one previous systemic treatment for melanoma.
MedDRA version: 13.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: RO5185426
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-

Primary Outcome(s)

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

Main Objective: To evaluate the safety and tolerability of RO5185426 in patients with metastatic melanoma (Stage IV; AJCC) harboring the BRAF V600 mutation.

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 (Stage IV, AJCC) harboring the BRAF V600 mutation (identified by the cobas 4800 BRAF V600 Mutation Test). Adverse events, all AEs, AEs grade 3 or 4, AEs of special interest (for example, SCC), AEs leading to
treatment interruption and discontinuation, serious adverse events (SAEs), dermatological evaluations and other assessments for SCC, premature discontinuation from study and treatment, laboratory parameters and study medication will be the primary safety variables.

Secondary ID(s)

MO25515

2010-023526-21-ES