E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
unresectable metastatic (stage IV)non-uveal melanoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025654 |
|
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 |
1. To establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of DTIC in patients with metastatic melanoma, the preliminary tolerability profile of the combination.
2. To evaluate objective response rate (ORR) at the end of induction |
|
E.2.2 | Secondary objectives of the trial |
1. To investigate the: Pharmacokinetics of L19IL2 and dacarbazine Induction of human anti-fusion protein antibodies (HAFA) Antitumor activity of L19IL2 with dacarbazine in patients with metastatic melanoma. 2. To estimate progression -free survival (PFS) To estimate overall survival (OS) To assess safety and tolerability |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed unresectable metastatic (stage IV) non-uveal melanoma Age > 18 years Measurable disease defined as at least one lesion that can be accurately and serially measured as per modified RECIST criteria. Prior therapy for metastatic melanoma: oPhase I dose escalation: prior therapy allowed, including prior chemotherapy; previous treatment with DTIC: patients should be treated > 6 months prior to study entry oPhase II : no prior therapy except radiation. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions ECOG performance status < 2 Life expectancy of at least 12 weeks Negative serum pregnancy test (for women of child-bearing potential only) at screening |
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E.4 | Principal exclusion criteria |
Primary ocular melanoma Evidence of brain metastasis Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry History of HIV infection or chronic hepatitis B or C Presence of active infections (e.g. requiring antibimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. Inadequately controlled cardiac arrhythmias including atrial fibrillation History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). Uncontrolled hypertension. Ischemic peripheral vascular disease (Grade Iib-IV). Severe diabetic retinopathy. Active autoimmune disease History of organ allograft or stem cell transplantation. Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment. Known history of allergy to IL2, dacarbazine, or other intravenously administered human proteins/peptides/antibodies. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. determination of the recommended dose of L19IL2 when administered in combination with a fixed dose of dacarbazine. the preliminary tolerability profile . 2. determination of objective response rate (ORR) at the end of induction |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
| |
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 | |
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 |