E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically confirmed unresectable metastatic (stage IV) non-uveal melanoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025671 |
E.1.2 | Term | Malignant melanoma stage IV |
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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 |
Phase IIa part: - 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. Phase IIb part: - To evaluate objective response rate (ORR) after 8 cycles (week 24) |
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E.2.2 | Secondary objectives of the trial |
Phase IIa part: To investigate the: - Pharmacokinetics of L19IL2, dacarbazine and 5-aminoimidazole -4 carboxamide (AIC). - Induction of human anti-fusion protein antibodies (HAFA) - Antitumor activity of L19IL2 with dacarbazine in patients with metastatic melanoma - Evaluation of the immunological activity of study treatment - Evaluation of extra domain B of fibronectin (ED-B FN) expression- optional in consenting patients Phase IIb part: - To estimate progression –free survival (PFS) - To estimate overall survival (OS) - To evaluate objective response rate (ORR) - To assess safety and tolerability.
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E.2.3 | Trial contains a sub-study | No |
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 per the RECIST criteria 1.1. Cutaneous lesions measuring at least 1 cm will be considered measurable. Prior therapy for metastatic melanoma: o Phase IIa – Dose definition: prior therapy allowed, including prior chemotherapy; previous treatment with DTIC: patients should be treated > 6 months prior to study entry o Phase IIb Step 1-Activity Evaluation: 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 o Phase IIb Step 2 – ≤ one prior therapy Fewer than 3 organs involved or cutaneous and/or subcutaneous metastasis only, for Phase IIb patients ECOG performance status < 2 Life expectancy of at least 12 weeks Sufficient hematologic, liver and renal function • LDH < 2.0 x ULN for Phase IIa patients and normal LDH for the Phase IIb ones. 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 metastases 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. 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 Anti-tumor therapy within 4 weeks of the administration of study treatment. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment. Phase 2b Step 2: more than one prior treatment Growth factors or immunomodulatory agents within 7 days of the administration of study treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase IIa: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of human L19IL2 in combination with dacarbazine in metastatic melanoma patients for whom dacarbazine is a suitable therapy according to the discretion of the principal investigator.
Phase IIb: To evaluate the objective response rate after induction (6cycles for Step1 and 8cycles for Step2) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 |
evaluation of the MTD and RD of a combination of L19IL2 and dacarbazine in Phase IIa |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
For Phase IIb Step2 it is a open labeled controlled randomized trial with parallel groups |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Dacarbazine the standard of care for metastatic melanoma which will be applied to arm 3 |
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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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 48 |
E.8.9.2 | In all countries concerned by the trial days | 0 |