E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study is an open label, multicenter phase IIa clinical trial which is designed as a pilot project in order to establish the efficacy and tolerability of Multiferon as a neoadjuvant treatment of locoregional metastases. |
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MedDRA Classification |
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 |
Overall response rate (clinical and radiological) after 4 weeks of treatment (CR + PR) according to immune-related response criteria (irRC). |
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E.2.2 | Secondary objectives of the trial |
- Disease control rate (CR + PR +SD) according to irRC - Rate of histopathological complete responses - Tolerability - Differences in gene expression in metastatic tissue before/after treatment - Dose dependency of effects - Changes of serum markers and PBMC subsets before/after treatment (optional translational side studies)
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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 |
Immunohistological studies for subtyping of the lymphocyte infiltrate in the tumor shall be performed in tumor specimens before and after therapy. Serum markers: A penal of autoimmune antibodies and cytokines will be quantified in serum before/after neoadjuvant treatment in a subset of patients. PBMC (Peripheral blood mononuclear cells) subtyping: a characterization of PBMC will be performed by FACS-Analysis before and after neoadjuvant treatment
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E.3 | Principal inclusion criteria |
a) Histologically proven cutaneous melanoma b) Clinical stage IIIB or IIIC (AJCC 2010) c) ≥ 18 years of age d) Presence of at least two metastases, not more than 10 metastases, and completely resectable e) Measurable disease (at least one lesion that can be accurately measured in two perpendicular diameters, with both dimensions >= 5mm f) ECOG performance status of 0/1 g) Patients with previous adjuvant recombinant interferon-α treatment of any dose are eligible if (i) treatment was stopped at least 1 month before start of treatment and (ii) no progression occurred during interferon-α treatment. h) No childbearing potential or negative pregnancy test within 14 days before inclusion in women with child bearing potential Women with childbearing potential must be using an effective method of contraception (Pearl-Index < 1, e.g. oral contraceptives, other hormonal contraceptives [vaginal products, skin patches, or implanted or injectable products], or mechanical products such as an intrauterine device or barrier methods [diaphragm, spermicides]) throughout the study and for up to 3 months after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. No men of fathering potential or men of fathering potential must be using an effective method of contraception to avoid conception throughout the study and for up to 3 months after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. i) Signed and dated informed consent informed consent before the start of specific protocol procedures
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E.4 | Principal exclusion criteria |
j) Mucous membrane or ocular melanoma k) Any evidence of distant metastasis (e.g. whole body CT-scan including brain scan within 4 weeks before inclusion) l) Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris). m) ALAT or ASAT > 2 x ULN n) Total bilirubin > 2 x ULN o) Creatinine > 2 x ULN p) Patients who have a history of depression requiring hospitalization q) Patients with seizure disorders requiring anticonvulsant therapy r) Any of the following abnormal baseline hematologic/laboratory values: Hb < 10g/dl WBC < 3.0x109 /l Platelets < 100x109 /l s) Presence of active autoimmune disease t) Concurrent systemic glucocorticoids or any other systemic immunosuppressive therapy u) Unwilling or unable to comply with the requirements of the protocol v) Known infection with HBV, HCV, HIV w) Pregnant or lactating women x) Unwillingness or inability to employ an effective barrier method of birth control throughout the study and for up to 3 months after end of treatment in female or male patients
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the overall response rate (clinical and radiological) after 4 weeks of treatment (CR + PR) according to immune-related response criteria (irRC). |
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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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 15 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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
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The end of study is defined as 4 weeks +/- 4 days after last application of study drug |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |