E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uveal melanoma liver metastases |
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E.1.1.1 | Medical condition in easily understood language |
Uveal melanoma liver metastases |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To evaluate if IHP increases the Overall survival compared to BAC. |
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E.2.2 | Secondary objectives of the trial |
Hepatic progression-free survival Response Health economic evaluation SAE |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria 1. Male or female aged above 18 years. 2. Signed and dated written informed consent before the start of specific protocol procedures. 3. Histologically or cytologically proven liver metastases of uveal melanoma. If this is not possible at the time of randomization, a biopsy is mandatory before start of treatment. 4. Liver metastases measurable by MRI (preferred) or CT of thorax and abdomen according to RECIST version 1.1 with at least one unidimensional measurable lesion ≥ 10 mm. The examination should be within 4 weeks prior to randomization. 5. ECOG performance status of 0 or 1. 6. No previous chemotherapy, radiotherapy, or biologic therapy for uveal melanoma metastases (ie first-line therapy) 7. Adequate hepatic function (defined as ASAT,ALAT, bilirubin <= 3*ULN and PK-INR <= 1.5) and no medical history of liver cirrhosis or portal hypertension |
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E.4 | Principal exclusion criteria |
1. More than 50% of the liver volume (measured by CT or MRI) replaced by tumour. 2. Evidence of extrahepatic disease by PET-CT 3. Life expectancy of less than 4 months 4. Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study. 5. Active infection. 6. Ischemic cardiac disease or history of congestive heart failure with an LVEF < 40%. 7. COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted for age. 8. Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula. 9. Reduced blood leukocytes or platelets defined as LPK < 2.0x109/L and TPK <100x109/L 10. Use of live vaccines four weeks before or after the start of study. Body mass index above 35. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival defined as the frequency of individuals alive at 24 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Median overall survival Hepatic progression-free survival Response Health economic evaluation SAE |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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
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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 | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |