E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recombinant Interleukin-21 administered subcutaneously for 4 weeks as neo-adjuvant treatment prior to sentinel lymph node/complete lymph node dissection followed by 8 weeks of adjuvant treatment in subject with stage III malignant 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 |
E.1.2 | Term | Malignant melanoma stage III |
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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 estimate the complete response rate of the sentinel lymph node(s) as assessed by histopathology in subjects with stage III malignant melanoma measured after 4 weeks of local neo-adjuvant treatment with recombinant interleukin-21 (rIL-21). |
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E.2.2 | Secondary objectives of the trial |
To describe the immune modulating effects of rIL-21 within the tumour draining lymph nodes and the peripheral blood. -To estimate relapse free servival. -To describe the safety of neo-adjuvant and adjuvant subcutaneous (s.c) administration of rIl-21 in subjects with stage III malignant melanoma -To assess if antibodies against rIL-21 are induced during therapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) 2.Confirmed histologically stage III malignant melanoma according to the American Joint Committee on Cancer (AJCC 2006) within the following classification: -T1-4b -N1-3 (assessed by high resolution ultrasound) -M0 3.At least one lymph node with only partial malignant involvement as assessed by ultrasonography 4.18 years of age or above 5.ECOG performance status of 0 or 1 6.Haematology: -White blood cell (WBC) ≥ 2.5 x 10^9/L -Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L -Platelet count ≥ 100 x 10^9/L -Haemoglobin ≥ 100 g/L 7.S-creatinine ≤ 1.8 mg/dL 8.Liver function: -ALT and Alkaline Phosphatase ≤ 2.5 x upper limit of normal (ULN) -LDH ≤ 2 x ULN
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E.4 | Principal exclusion criteria |
1.Known or suspected allergy to trial product(s) or related products 2.Previous participation in this trial. Participation is defined as screening 3.Any signs of stage IV disease according to AJCC 2006 as assessed by routine radiographic staging 4.Prior wide excision of the primary lesion 5.Bulky lymph nodes metastases larger than 2 cm in longest diameter as assessed by ultrasonography 6.Clinically significant infection in the area of the primary tumour 7.Documented positive serologic testing for hepatitis B or C 8.History of or active presence of auto-immune diseases (except vitiligo and treated pernicious anaemia) 9.History of any other active malignancy incl. ocular malignant melanoma (except basal cell carcinoma of the skin and cervical cancer in situ) within 5 years of enrolment 10.Cardiac disease within the last 12 months defined as: -decompensate heart failure (New York Heart Association (NYHA) class III or IV) -serious arrhythmias -unstable angina pectoris -myocardial infarction 11.Concurrent treatment with systemic corticosteroids or other immunosuppresive drugs (topical or inhaled corticosteroid treatment is permitted) 12.Known chronic infectious disease including human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) related illness 13.Any significant systemic disease which according to the Investigator could compromise the safety of the subject or interfere with the trial objectives 14.Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures are implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence, or vasectomised partner) 15.The receipt of any investigational drug within 3 months prior to this trial 16.Location of the primary lesion where multiple injections of rIL-21 are not possible
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E.5 End points |
E.5.1 | Primary end point(s) |
•Complete pathological response rate defined as the percentage of subjects identified with lack of detectable malignant disease in the dissected sentinel lymph nodes after a 4-week neo-adjuvant rIL-21 treatment period and assessed according to the EORTC Melanoma Group protocol for SLN examination. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |