E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
unresectable advanced melanoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 5.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027150 |
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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 determine the efficacy of plitidepsin, alone or in combination with dacarbazine, in the front-line treatment of subjects with unresectable advanced melanoma
To determine the MTD and RD of plitidepsin administered in combination with dacarbazine to patients with advanced unresectable melanoma |
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E.2.2 | Secondary objectives of the trial |
To further study the pharmacokinetics of plitidepsin, including drug-drug pharmacokinetic interactions between plitidepsin and dacarbazine
To evaluate the safety and tolerability of plitidepsin, administered alone or in combination with dacarbazine, as front-line therapy of subjects with unresectable advanced melanoma |
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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 |
Full title: GENE EXPRESSION PROFILING STUDIES USING TUMOUR TISSUE OF PATIENTS WITH MELANOMA INCLUDED IN THE CLINICAL STUDY APL-B-016-05
Objectives: 1. Determine the gene expression profiles of tumour tissue of the patients with melanoma included in the clinical study APL- B-016-05. 2. Correlate the gene expression profiles with the clinical outcome of the patients and the evolution of the disease. 3. Validate in patient tumour samples selected putative markers of sensitivity to plitidepsin ± DTIC found in in vitro studies |
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E.3 | Principal inclusion criteria |
1.Voluntary written informed consent 2.Malignant melanoma histologically proven 3.Advanced melanoma 4.Age from 18 years 5. measurable disease 6.Recovery from any non-hematologic drug-related adverse event derived from previous treatment 7.Laboratory values within 14 days prior to first infusion: ·Aspartate aminotransferase (AST) ≤ 2.5 x ULN ·Alanine aminotransferase (ALT) ≤ 2.5 x ULN 8.Performance status 9.Life expectancy > 3 months 10.Left ventricular ejection fraction (LVEF) within normal limits 11. negative serum pregnancy and Acceptable methods of contraception
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E.4 | Principal exclusion criteria |
1. prior systemic therapy for the treatment of metastatic melanoma 2.Subjects relapsing / progressing within 6 months after the end of adjuvant or neo-adjuvant systemic drug therapy for non-metastatic melanoma 3. loco-regional melanoma previously treated with loco-regional drug therapy with disease relapse or progression within the treated area 4.Subjects for whom surgery would be expected to result in cure or significant palliation 5.Less than 4 weeks from radiation therapy 6.Evidence of progressive CNS metastases or any symptomatic brain or leptomeningeal metastases 7.Other relevant diseases or adverse clinical conditions: . History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure ·Previous mediastinal radiotherapy ·Uncontrolled arterial hypertension despite optimal therapy ·Any grade of Cardiac arrhythmia according to CTCAE v3.0 (see Appendix 6) 8.Pregnant or lactating women 9.Limitation of the patient’s ability to comply with the treatment or follow-up procedures and visits defined in the study protocol 10.Known hypersensitivity to any component of the study drug products, including plitidepsin, dacarbazine, cremophor, mannitol, citrate, or ethanol
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E.5 End points |
E.5.1 | Primary end point(s) |
· Efficacy · Dose limiting toxicities |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
combination study with dacarbazin |
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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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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The predefined date of study termination (clinical cut-off) is 6 months after the last patient discontinuation |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |