E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line therapy for adult patients with histologically confirmed metastatic melanoma (unresectable Stage IIIC or Stage IV) harbouring the V600E positive mutation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
• 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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
RCR project asociated to the main protocol (please see version of protocol in the section A.4 of the application form. Tha specimens in the RCR will be made available for future biomarker research toward further understanding of RO5185426 treatment of melanoma, related diseases and adverse events and for the development of potential associated diagnostic assays. |
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E.3 | Principal 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) |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.6.13.1 | Other scope of the trial description |
Tumour assessments, performance status, quality of life, physical symptoms improvement, biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end when all patients enrolled have been followed until death, withdrawal of consent, or lost to follow up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |