E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uveal Melanoma (requiring enucleation) |
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E.1.1.1 | Medical condition in easily understood language |
Cancer (melanoma) of the eye |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025654 |
E.1.2 | Term | Malignant melanoma of sites other than skin |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 determine the safety and efficacy (effectiveness) of intravitreal Ranibizumab, in the neoadjuvant (before surgery) setting, in high risk ocular melanoma patients. |
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E.2.2 | Secondary objectives of the trial |
To describe the toxic effects of intravitreal Ranibizumab in high risk ocular melanoma patients. To explore relationships between ultrasonographic response, serum and intravitreous VEGF levels, and the gene expression profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Confirmed diagnosis of uveal melanoma requiring enucleation 2) Must have ultrasonographically documented measurable disease within 4 treatment according to the WHO criteria 3) Prior treatments with chemotherapeutic or antiangiogenic agents for other malignancies are allowed after 6 months of discontinuation 4) Age ≥ 18 years 5) Performance Status ≤2 6) Previous or present vascular intraocular diseases not requiring use of antiangiogenic agents will be allowed 7) Laboratory results: Hb ≥ 10g/dl Platelets ≥ 100,000mm3 WCC ≥ 3.0 x 109/L ANC ≥ 1.0 x 109/L Bilirubin < twice normal, Alkaline Phosphatase < 5 x normal INR ‹ 2 Cr ≤ 1.5 ULN 8) Normal blood pressure or controlled hypertension. 9) No recent major surgical procedures (laparotomy or thoracotomy) within 4weeks. 10) No thromboembolic event within 6 months 11) No known coagulopathy disorder. 12) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. 13) Before patient registration, written informed consent must be given according to ICH/GCP, and national regulations. |
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E.4 | Principal exclusion criteria |
1) Serious underlying medical condition according to the judgement of the Principal Investigator 2) Pregnant or nursing patients 3) Inability to provide adequate informed consent. 4) Hypersensitivity to the active substance or to any of the excipients. 5) Active or suspected ocular or periocular infections. 6) Active severe intraocular inflammation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine response rate of intravitreal Ranibizumab, in the neoadjuvant setting, in large primary ocular melanoma patients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All patients having completed the T28 tumour assessment after first intravitreal Ranibizumab injection. |
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E.5.2 | Secondary end point(s) |
To describe the toxic effects of intravitreal Ranibizumab in high risk ocular melanoma patients. To explore relationships between ultrasonographic response, serum and intravenous VEGF levels, and gene expression profile. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The last patient completing the final follow-up visit(6 month) |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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
|
Last Patient Last visit (6 month follow-up) |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 30 |