E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
c-KIT mutated advanced acral or mucosal melanoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 10 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025654 |
E.1.2 | Term | Malignant melanoma of sites other than skin |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 10 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000583 |
E.1.2 | Term | Acral lentiginous melanoma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and effectiveness of the drug nilotinib in the treatment of acral and mucosal melanomas which have mutations in a cell surface protein known as c-KIT. |
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E.2.2 | Secondary objectives of the trial |
To investigate the biology of response and resistance to nilotinib treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria 1. Patients with c-KIT mutated histologically proven advanced mucosal or acral melanoma in which the mutation is not known to be associated with nilotinib resistance. 2. Unresectable locally advanced or metastatic disease 3. The presence of one or more clinically or radiologically measurable lesions at least 10mm in size 4. ECOG performance status 0, 1 or 2 5. Life expectancy greater than 12 weeks 6. At least 28 days since major surgery and 7 days since skin/tumour biopsy 7. The capacity to understand the patient information sheet and the ability to provide written informed consent 8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures 9. Age 18 or greater 10. Women must be postmenopausal (no menstrual period for a minimum of 1 year) or have a negative serum pregnancy test on entry in the study (even if surgically sterilised). Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last study treatment 11. Serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), total serum bilirubin ≤1.5 x ULN 12. Serum creatinine ≤1.5 x ULN 13. Haemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5 x 109/L, platelets ≥100 x 109/L 14. Prothrombin time (PT) ≤1.5 x ULN
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E.4 | Principal exclusion criteria |
Exclusion Criteria 1. Intracranial disease, unless there has been radiological evidence of stable intracranial disease > 6 months. In the case of a solitary brain metastasis, evidence of a disease-free interval of at least 3 months post surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days 2. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last treatment 3. Men who plan to father a child within 6 months of the last treatment 4. Use of any investigational drug within 30 days prior to screening 5. Significant cardiac disease including patients who have or who are at significant risk of developing prolongation of QTc 6. Severe and/or uncontrolled medical disease 7. Known chronic liver disease 8. Known HIV infection 9. Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy in the 4 weeks prior to study entry 10. Prior exposure to a tyrosine kinase inhibitor
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of participants progression free at 6 months.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | 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 | 9 |
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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30 days after the last trial participant receives the last dose of the investigational medicinal product. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |