E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with metastatic (stage IV) melanoma will be randomized to either treatment arm A (dacarbazine) or treatment arm B (TIL) after metastasectomy and feasibility of culturing of TIL. |
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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 | 10053571 |
E.1.2 | Term | Melanoma |
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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 |
Feasibility study (n=5 patients) To examine whether the logistics and timing of this complex treatment can be managed properly without delays for the patients. If necessary this will be optimized before starting the RCT. In addition, toxicity (according CTCAE v. 3.0) and response rate (according RECIST version 1.1) will be measured.
Randomized phase II clinical trial: Primary objective: Improvement of progression free survival compared to standard dacarbazine chemotherapy
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E.2.2 | Secondary objectives of the trial |
Randomized phase II clinical trial: Secondary objective(s): Objective response rate according to RECIST version 1.1, 1-year PFS, median overall survival, toxicity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size (≥ 3 cm) and must be willing to undergo such a resection for experimental purposes. • Patients must be ≥ 18 years of age and must have measurable metastatic melanoma (in addition to the resected lesion). • Patients must have a clinical performance status of ECOG 0 or 1. • Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen. • Patients must be able to understand and sign the Informed Consent document. Laboratory Parameters (Note: patients may undergo resection with lab values outside of the parameters listed below if it is anticipated that the resection will correct the abnormality). • Hematology: Absolute neutrophil count greater than 1.5 x 109/L without support of filgrastim. Platelet count greater than 100 x 109/L. Hemoglobin greater than 5 mmol/L. • Chemistry Serum ALAT/ASAT less than 3 times the upper limit of normal, unless patients have liver metastases (< 5 times ULN). Serum creatinine clearance 50 ml/min or higher. Total bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert’s Syndrome who must have a total bilirubin less than 50 micromol/L. • Serology: Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) Seronegative for hepatitis B antigen, and hepatitis C antibody. Seronegative for lues.
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E.4 | Principal exclusion criteria |
• Life expectancy of less than three months. • Patients with metastatic ocular or mucosal melanoma. • Requirement for systemic steroid therapy. • Patients who have a history of more than two CNS metastases. • Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or shows significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months. • Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks. • The following patients will be excluded because of inability to receive high dose interleukin-2: History of coronary revascularization Documented LVEF of less than 45% in patients with: Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2° or 3° heart block Documented FEV1 less than or equal to 60% predicted for patients with: A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years) Symptoms of respiratory distress • All patients’ toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less. • Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. • Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the randomized controlled phase II trial is PFS improvement from 2 months in DTIC arm to 6 months in the TIL treatment arm. |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
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.8.5 | 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 | 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 | 4 |
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 | 4 |
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 |