| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced or metastatic BRAF V600E/K mutation-positive melanoma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027481 |
|
| 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 |
| The primary objective for this study is to establish the superiority of GSK1120212 over chemotherapy with respect to progression-free survival for subjects with advanced/metastatic BRAF V600E/K mutation-positive melanoma. |
|
| E.2.2 | Secondary objectives of the trial |
| To further characterize the efficacy in the total population with respect to overall survival, overall response rate, and duration of response. To characterize PFS in the subgroup of subjects that have received no prior chemotherapy in the advanced or metastatic setting and the subgroup who have received one prior chemotherapy in the advanced or metastatic setting. To characterize PFS and overall response rate in the subgroup of subjects with BRAF V600 K mutation-positive melanoma. To characterize efficacy (PFS, overall response rate, and duration of response)in subjects following crossover from chemotherapy to GSK1120212. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Signed written informed consent. ≥18 years of age.Histologically confirmed, Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory.Subjects may have received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy |
|
| E.4 | Principal exclusion criteria |
| Any prior use of: a. BRAF inhibitors or MEK inhibitors. b. Ipilimumab in the advanced or metastatic setting. Subjects who have received dacarbazine or paclitaxel prior to randomization will not be eligible to receive the same chemotherapy as study medication (i.e. a subject who received prior dacarbazine cannot receive dacarbazine on this trial and would thus receive paclitaxel if randomized to the control arm).Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy or immunotherapy within the last 21 days. Chemotherapy given daily or weekly without the potential for delayed toxicity within the last 14 days. Administration of an investigational drug within 28 days or 5 half-lives,(whichever is shorter), prior to randomization – at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and randomization.Current use of any prohibited medication (see Section 6). Use of anticoagulants such as warfarin is permitted, however INR must be monitored in accordance with local institutional practice.History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above.Any serious and/or unstable pre-existing medical (aside from malignancyexception above), psychiatric disorder, or other conditions that could interferewith subject’s safety, obtaining informed consent or compliance to the studyprocedures.Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed). Brain metastases with the following exceptions that are ALL confirmed by theGSK Medical Monitor: c. All known lesions must be previously treated with surgery or stereotactic radiosurgery, and d. Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for ≥90 days prior to randomization (must be documented with two consecutive MRI or CT scans using contrast), and c. Asymptomatic with no corticosteroids requirement for ≥ 30 days prior to randomization, and e. No enzyme-inducing anticonvulsants for ≥ 30 days prior to randomization. History or evidence of cardiovascular risk including any of the following: f. QTcB ≥ 480 msec. g. History or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible. h. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization. i. History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association. History of interstitial lung disease or pneumonitis. History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): • History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study will be progression free survival based on investigator assessments, defined as the time from randomization until the earliest date of disease progression or death due to any cause. Investigator assessments will be used as it serves as a direct measure of the effect of randomized treatment. A blinded, independent, central review will be performed. Analyses of PFS based on BIRC assessments will be considered supportive. |
|
| 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 | 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 | Yes |
| 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 | 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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 |
|
| 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
|
| Finestudio:LPLV.Il FU di sopravvivenza fino a quando l`80% dei soggetti sara` deceduto o avra`abbandonato il FU. I soggetti responder in trattamento con GSK1120212 al momento del completamento dello studio entreranno in un roll-over protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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