E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Melanoma with Brain Metastases |
|
E.1.1.1 | Medical condition in easily understood language |
Metastatic Melanoma with Brain Metastases |
|
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 efficacy of vemurafenib using Best Overall
Response Rate (BORR), as assessed by an Independent
Review Committee (IRC) using Response Evaluation Criteria
in Solid Tumors, Version 1.1 (RECIST, v1.1) in the brain of
metastatic melanoma patients with previously untreated brain
metastases |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of vemurafenib using BORR in the brain of patients with previously treated or untreated brain metastases assessed by an IRC using RECIST v1.1 criteria
• To evaluate the efficacy of vemurafenib using BORR in the brain of patients with previously-treated brain metastases as assessed by an IRC using RECIST v1.1 criteria
• To evaluate the safety and tolerability of vemurafenib in patients with melanoma metastatic to the brain, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0)
• To evaluate BORR outside of the brain as assessed by an IRC, duration of response (DOR) in and outside of the brain, progression-free survival (PFS), time to development of new brain metastases in responding patients, and overall survival (OS) in patients with melanoma metastatic to the brain
• To evaluate the efficacy of vemurafenib using BORR in the brain and outside of the brain |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Adult patients, ≥ 18 years of age
•Metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
•Measurable brain metastases, treated or untreated
•Patients may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
•Patients may or may not have symptoms related to their brain metastases
•Eastern Cooperative Oncology Group (ECOG) performance status 0-1
•Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
|
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E.4 | Principal exclusion criteria |
•Increasing corticosteroid dose during the 7 days prior to first dose of study drug
•Leptominingeal involvement in patients with no prior treatment for brain metastases (cohort 1). Leptomeningeal involvement is only allowed in patients with prior treatment for brain metastases (cohort 2)
•Previous malignancy requiring active treatment 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 anticancer therapies other than those administered in the study
•Treatment with any cytotoxic and/or investigational cytotoxic drug or targeted therapy ≤ 4 weeks prior to first administration of vemurafenib and radiation therapy ≤ 1 weeks prior to first administration of vemurafenib and stereotactic radiotherapy ≤ 1 day prior to prior to first administration of vemurafenib.•Prior treatment with BRAF or MEK inhibitors
•Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug
•History or presence of clinically significant cardiac dysrhythmia
•Corrected QT interval ≥ 450 ms or history of congenital long QT syndrome
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Best Overall Response Rate (BORR) in previously untreated brain metastases (assessed by Independent Review Committee using RECIST) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•BORR in previously treated or untreated brain metastases (assessed by Independent Review Committee)
•BORR in previously treated brain metastases (assessed by Independent Review Committee)
•BORR outside of the brain (assessed by Independent Review Committee)
•BORR in brain metastases and outside of the brain (assessed by Investigator)
•Duration Of Response, Progression Free Survival, time to development of new brain metastases, Overall Survival
•Safety (assessed by NCI CTCAE)
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
QUALITY OF LIFE AND PHYSICAL SYMPTOMS |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Australia |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
|
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
|
The end of study will occur when all patients have been followed up for survival for a maximum period of 24 months, have died, withdraw consent or are lost to follow up, whichever occurs first |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |