The trial is planned in a neo-adjuvant setting for a 4-weeks period in Melanoma patients with stage III. The stage is to be discovered by ultrasound and veriefied by fine needle punctere and cytology.
Conditions
Interventions
Trade Name: Proleukin
Pharmaceutical Form: Solution for infusion
Sponsors
Klinik für Dermatologie, Venerologie und Allergologie; Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 (by histology of the primary and FNAC/cytology of the involved lymph node) stage III malignant melanoma according to the American Joint Committee on Cancer (AJCC 2009) within the following classification: a. T1-4b b. N1-3 (assessed by high resolution ultrasound and FNAC) c. M0 3. At least one lymph node with only partially malignant involvement as assessed by ultrasound 4. 18 years of age or above 5. ECOG performance status of 0 or 1 6. Hematology: a. White blood cell (WBC) = 2.5 x 109/L b. Absolute neutrophil count (ANC) = 1.5 x 109/L c. Platelet count = 100 x 109/L d. Hemoglobin = 100 g/L 7. Serum-creatinine = 1.8 mg/dL 8. Liver function: a. ALT and Alkaline Phosphatase = 2.5 x upper limit of normal (ULN) b. LDH = 2 x ULN Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Known or suspected allergy to trial product(s) or related products 2. Any contraindication as listed in the product label for IL-2 (Proleukin®, Aldesleukin) 3. Previous participation in this trial. (Participation is defined as screening) 4. Any signs of stage IV disease according to AJCC 2009 as assessed by routine radiographic staging5. Prior wide excision of the primary lesion, which in the opinion of the investigator may alter lymphatic flow to the sentinel lymph nodes 6. Bulky lymph nodes metastases, which in the opinion of the investigator may completely obstruct lymphatic flow to the regional lymph nodes, as assessed by ultrasound 7. Clinically significant infection in the area of the primary tumour 8. Documented positive serologic testing for hepatitis B or C 9. History of or active presence of auto-immune diseases (except vitiligo and treated pernicious anemia) 10. 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 11. Cardiac disease within the last 12 months defined as: a) decompensated heart failure (New York Heart Association (NYHA) class III or IV) b) unstable angina pectoris c) serious arrhythmias d) myocardial infarction 12. Concurrent treatment with systemic corticosteroids or other immunosuppressive drugs (topical or inhaled corticosteroid treatment is permitted) 13. Known chronic infectious disease including human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) related illness 14. Any significant systemic disease which according to the Investigator could compromise the safety of the subject or interfere with the trial objectives 15. 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, barrier methods, sexual abstinence or vasectomised partner) 16. The receipt of any investigational drug within 3 months prior to this trial 17. Location of the primary lesion where multiple injections of s.c. IL-2 are not feasible
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Following 4 weeks of neo-adjuvant treatment with IL-2;Main Objective: To estimate the complete response rate of the SLNB/CLND specimens, as assessed by histopathology in subjects with stage III malignant melanoma measured after 4 weeks of local neo-adjuvant treatment with IL-2.;Secondary Objective: *To describe immune modulating effects of IL-2 within the tumour draining lymph nodes and peripheral blood: -- morphological and functional changes of lymph nodes assessed by ultrasound --Comparing fine needle aspirates in the affected lymph nodes before and after IL-2 treatment (qRT-PCR) of a selected panel of genes specific for T cells, B cells, NK cells as well as various cytokines, effector molecules, chemokines and receptors --relative frequency of cells staining for markers of T cells, B cells, NK cells and dendritic cells in the resected lymph nodes as measured by immuno-histo chemistry (IHC) staining --Relative frequency of absolute numbers of blood cells (incl. T cell subtypes and B cells) as measured by flow cytometry of peripheral mononuclear blood cells (PBMC) --Describing levels of soluble CD25 and other serum markers **To describe the safety of local neo-adjuvant subcutaneous IL-2 administration ***To estimating relapse free survival;Primary end point(s): Complete pathological response rate defined as the fraction of subjects observed with complete absence of metastatic deposits in the SLNB/CLND specimens after a 4-week neo-adjuvant IL-2 administration as assessed according to the EORTC Melanoma Group protocol for SLN examination | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Ultra-sonographic assessments of the relevant lymph nodes •Signs of malignant deposits in lymph node specimens •Gene expression detected in the FNA by qRT-PCR of relevant genes •Immunohistochemical assessment of lymph node specimens •Assessment of various proteins detected in serum, including soluble CD25 •Relapse free survival •Incidence and severity of adverse events observed during the trial ;Timepoint(s) of evaluation of this end point: Ultrasonography (weeks 1, 2, 3 and 4); Signs of malignant deposits (week 4); Gene expression in FNA (week 0 and 4); IHC (week 4); serum markers (week 1, 2, 3, 4, 5 and 8); adverse events (week 1, 2, 3, 4, 5 and 8); relapse free survival (up to year 4 after trial) | — |
Countries
Germany
Contacts
Public ContactHauttumorcentrum
Charité - Universitätsmedizin Berlin
Outcome results
None listed