E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with stage III/IV melanoma |
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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 | 10025670 |
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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 | 10025671 |
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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 |
Rate of patients with complete response (CR) of L19IL2 treated metastases at week 12 |
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E.2.2 | Secondary objectives of the trial |
Safety of intratumoral administration of L19IL2 Rate of patients with CR, partial response (PR) and stable disease (SD) of L19IL2 treated metastases at week 12 (objective response rate and disease control rate of L19IL2 treated metastases) Duration of objective response and disease control of L19IL2 treated metastases Rate of patients with CR, PR and SD of all metastases at week 12 (objective response rate and disease control rate of all metastases) Duration of objective response and disease control of all metastases Overall survival (OS) Quality of life |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histopathologically proven malignant melanoma • Presence of measurable and injectable soft tissue metastases either in clinical stage III or stage IV M1a without visceral metastases. • Males or females, age > 18 years • Either without or after one line of prior systemic treatment for metastatic disease. • ECOG performance status < 2 • LDH < 2 x the upper limit of normal • Life expectancy of at least 12 weeks • Absolute neutrophil count > 1.5 x 109/L • Hemoglobin > 9.0 g/dL • Platelets > 100 x 109/L • Total bilirubin ≤ 30 �mol/L (or ≤ 2.0 mg/dl) • ALT and AST ≤ 2.5 x the upper limit of normal (ULN) (5.0 x ULN for patients with hepatic involvement with tumor) • Serum creatinine < 1.5 x ULN • All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.02) Grade ≤ 1 unless otherwise specified above • Negative serum pregnancy test (for women of child-bearing potential only) at screening • If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug. • Able to provide written Informed Consent. • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. |
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E.4 | Principal exclusion criteria |
• Primary ocular melanoma • Presence of visceral metastases at screening • Evidence of active brain metastases at screening. • 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 infectious hepatitis B or C • Presence of active infections (e.g. requiring antimicrobial 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. • Inadequately controlled cardiac arrhythmias including atrial fibrillation • 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, or other intravenously administered human proteins/peptides/antibodies. • Breast feeding female • Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery). • Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment. • Growth factors or immunomodulatory agents within 7 days of the administration of study treatment • Patients in need of systemic treatment for rapidly progressive systemic disease during study treatment and up to 2 weeks after injection of L19IL2. • Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion. • Any conditions that in the opinion of the investigator could hamper compliance with the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints of the study is the rate of patients with complete response (CR) of L19IL2 treated metastases at week 12. A 95% confidence interval will be provided. |
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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 | 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) | 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 | 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 |
Studio di fase II, non randomizzato, multicentrico e prospettico |
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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.8.4.1 | 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 | 5 |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |