E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hepatic metastases in patients with a carcinomatous primary tumor other than hepatocellular (HCC), biliary or bile duct carcinoma |
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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 | 10027457 |
E.1.2 | Term | Metastases to liver |
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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 |
To assess the pharmacokinetic profile of EndoTAG-1 (22mg/m²) after single-dose and in steady-state
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E.2.2 | Secondary objectives of the trial |
-To assess the effect of EndoTAG-1 on target liver metastases perfusion and vascular permeability -To assess the effect of EndoTAG-1 on soluble blood markers of angiogenesis -To assess the correlation between metastases perfusion and the pharmacokinetic profile -To gain further safety data |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Unresectable hepatic metastases of a carcinomatous origin with exception of HCC, biliary or bile duct carcinoma 2. At least one measurable hepatic metastasis > 20 mm in diameter (measured in MRI) 3. Last application of palliative chemotherapy (drug dependent on the primary tumor) at least 7 days ago 4. Gender: male and female (at least 6 individuals of each gender) 5. Age ≥ 18 years 6. Negative pregnancy test (females of childbearing potential) 7. Willingness to perform double-barrier-contraception during the study and for 6 month post study medication 8. ECOG performance status 0, 1 or 2 9. Assumed expectancy of life > 3 month 9. Signed informed consent
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E.4 | Principal exclusion criteria |
1. History of significant liver pathology (other than metastases, e.g. cirrhosis of the liver, PSC, PBC) or liver transplantation 2. Laboratory tests (hematology, chemistry) outside specific limits: -ANC ≤ 1.0 x 10^9/L -Platelets ≤ 100 x 10^9/L -Hb ≤ 9.0 g/dL (≤ 5.6 mmol/L) -Total Bilirubin > 2.0 mg/dL -Serum Creatinine > 1.5 mg/dL 3. Renal insufficiency with a GFR < 60 mL/min 4. Currently ongoing taxane-containing palliative chemotherapy regimen or history of taxane administration within 4 weeks prior to randomization 5. Pregnancy or nursing status 6. Positive HIV, HBV or HCV testing 7. The patient has a contraindication for MRI ôr CEUS according to accepted clinical guidelines 8. Known hypersensitivity to any component of the EndoTAG®-1 formulation or gadolinium-based MR-contrast media or sulphur hexafluoride 9. Claustrophobia or history of active or significant neurological disorder and/ or psychiatric disorder that would prohibit the understanding and giving of informed consent, or would interfere in the clinical and radiological evaluation of the patient during the trial 10. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry
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E.5 End points |
E.5.1 | Primary end point(s) |
-Pharmacokinetic profile: C max, t max, t ½ term, AUC 0-t, AUC 0-inf, VD and CL for paclitaxel, 6α-OH-paclitaxel and DOTAP
•Secondary endpoints: - Kep, Ktrans, iAUC60, iAUC90 and iAUC120, of dynamic blood flow in target hepatic metastases and ADC: Number of subjects with decrease, no change or increase between Screening (Baseline) and all post baseline time points measured in DCE-MRI
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | |