E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10027481 |
E.1.2 | Term | Metastatic 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 |
The primary objective is to assess the efficacy of IPH1101/IL-2 in monotherapy and in combination with Dacarbazine in advanced melanoma patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To determine the safety of IPH1101/ IL-2 association alone and in combination with dacarbazine - To assess the biological activity of the treatment - To investigate the relationship between biological activity and efficacy of the treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female aged over 18 years, 2) Histologically confirmed diagnosis of melanoma, 3) Stage IV disease or unresectable stage III c (AJCC ), 4) Measurable disease according to modified RECIST criteria defined as at least 1 malignant lesion that could be accurately and serially measured in at least 1 dimension and for which the greatest diameter is > or = 10 mm as measured by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), or > or = 20 mm with conventional techniques. A caliper can be used for the measurement of superficial cutaneous metastases which are > or = 10 mm; 5) Patient who has never been treated by chemotherapy previously, 6) ECOG performance status < 1, 7) Serum lactate dehydrogenase (LDH) < 1,1 x ULN, 8) At least 4 weeks since major prior surgery, 9) QTc interval duration < 430 ms for men, < 450 ms for women, 10) Adequate bone marrow, hepatic and renal function as follows: - Lymphocytes > ou = 0.9 109/L - Platelets > ou 100 x 109/L, - Total bilirubin < ou = 2 x upper limit normal (ULN) - Transaminases (AST [SGOT]; ALT SGPT]) < ou = 3 x ULN - Serum creatinine < ou = 2.0 mg/dL or calculated creatinine clearance > 60mL/min; 11) Male or female patient who accepts and is able to use recognised highly effective contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) throughout the study and during 3 months after the end of treatment; 12) Signed informed consent prior to any protocol-specific procedures.
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E.4 | Principal exclusion criteria |
1) Primary ocular or mucosal melanoma; 2) Presence of any brain metastasis; 3) Concurrent treatment with any other anti-cancer therapy or any forbidden concomitant treatments; 4) Participation in another clinical trial with any investigative drug within 30 days prior to study randomization; 5) Prior history of high dose chemotherapy followed by bone marrow or peripheral stem cell support or presence of transplanted solid organ (with the exception of corneal transplant > 3 months prior to study randomization); 6) Any known hypersensitivity to one of the study treatments; 7) Any active auto-immune disease including the insulin-dependent diabetes or an immunodeficiency. The vitiligo is not an exclusion criterion; 8) Current active infection on the day of inclusion and judged serious by the investigator including viral infection HIV, HCV, HBV (HBsAg); 9) Serious concurrent, uncontrolled medical disorder such as diabetes; 10) Cardiovascular disease: -Stage III or IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure. Note: patients with NYHA stage I or II CHF may be included provided they do not have arrhythmia requiring treatment or fulfil any other exclusion criteria; -Myocardial infarction within the previous 6 months, or -Symptomatic cardiac arrhythmia requiring treatment; 11) History of another malignancy within the past 5 years, except basal cell carcinoma of the skin or carcinoma in situ of the cervix; 12) Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before request for randomization in the trial; 13) Pregnant or lactating women.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the evaluation of the objective response rate according to modified RECIST criteria. The objective response rate will be presented along with a 90% confidence interval in each 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 | Information not present in EudraCT |
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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 | Yes |
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) | 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
| Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 7 |
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 | 7 |