E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically confirmed metastatic melanoma harboring the BRAF V600 mutation as determined by the cobas® 4800 BRAF V600 Mutation Test. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with metastatic melanoma harboring the BRAF V600 mutation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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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 the safety and tolerability of RO5185426 in patients with metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) harboring the BRAF V600 mutation |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of RO5185426 as objective response rates (ORRs) determined by the investigator (RECIST, Version 1.1) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients ≥ 16 years of age
- Histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) with BRAF V600 mutation determined by Cobas 4800 BRAF Mutation Test
- Patients may or may not have received prior therapy for metastatic melanoma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate hematologic, renal and liver function.
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E.4 | Principal exclusion criteria |
- Evidence of symptomatic CNS lesions
- Previous malignancy (other than melanoma) within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
- Concurrent administration of any anti-cancer therapies other than those administered in the study
- Known hypersensitivity to RO5185426 or another BRAF inhibitor
- Clinically significant cardiovascular disease or event within the 6 months prior to first administration of study drug
- Refractory nausea or vomiting, external biliary shunt, or significant bowel resection that would preclude adequate absorption
- Evidence of symptomatic CNS lesions as determined by investigator, use of steroids or anti-seizure medications for treatment of brain metastases prior to the first administration of RO5185426 |
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E.5 End points |
E.5.1 | 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) harboring 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 tumor response, duration of response, progression free survival (PFS) and overall survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 190 |
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 | No |
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 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
Please refer to section 3.1.3 in the protocol. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |