E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Prostate Carcinoma
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
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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 determine the safety and efficacy of Yondelis®(trabectedin) treatment in metastatic prostate carcinoma
In Cohort A: To measure PSA response in men with AIPC treated with Yondelis®
In Cohort B: To measure PSA response, duration of response, and time to progression in an additional cohort of 16 prostate cancer subjects previously treated with docetaxel that will be treated with YONDELIS® administered by a 24-h infusion every 3 weeks
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E.2.2 | Secondary objectives of the trial |
In Cohort A: To assess the safety of administration of Yondelis® as a weekly, three-hour infusion in this population of patients. To measure , duration of response and time to progression in men with AIPC treated with Yondelis®. In Cohort B: To assess the safety of administration of Yondelis® as a 24-hours infusion every three weeks in these subjects
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
In Cohort A: . Signed informed consent · Histologically confirmed adenocarcinoma of the prostate · Radiographically documented metastatic disease · Surgical or chemical castration · PSA > 5 ng/ml · Androgen-independent disease, as defined by detectable, rising PSA in two consecutive measurements at least one week apart, with a minimum increment of at least 5 ng/ml above the nadir · No more than one previous chemotherapy regimen · ECOG/WHO performance status of 0, 1 or 2 · Adequate bone marrow reserve(s): - Neutrophil count > 1,500/ ml - Platelet count > 100,000/ ml · Adequate hepatic function: - Serum bilirubin < 1.0 x upper limit of normal - Serum alkaline phosphatase < 1.5 x upper limit of normal NOTE: If serum alkaline phosphatase is elevated, measurement of 5’ nucleotidase (5’NT) and gamma glutamyl transferasa (GGT) or alkaline phosphatase liver fraction should be performed, and if either of these is within normal limits (suggesting bone origin of abnormal alkaline phosphatase), patient may be included. - AST, ALT < 2.5 x upper limit of normal - Albumin > 2.5 g/dl · Adequate renal function, with serum creatinine < 1.5 x ULN
In Cohort B · Signed informed consent · Histologically confirmed adenocarcinoma of the prostate · Radiographically documented metastatic disease · Surgical or chemical castration · PSA > 5 ng/ml · Androgen-independent disease, as defined by detectable, rising PSA in two consecutive measurements at least one week apart, with a minimum increment of at least 5 ng/ml above the nadir · Previous treatment with one docetaxel based chemotherapy regimen · ECOG/WHO performance status of 0, 1 or 2 · Adequate bone marrow reserve(s): - Neutrophil count > 1,500/ μl - Platelet count > 100,000/ μl - Adequate hepatic function: - Serum bilirubin < 1.0 x upper limit of normal - Serum alkaline phosphatase < 1.5 x upper limit of normal - NOTE: If serum alkaline phosphatase is elevated, measurement of 5’ nucleotidase (5’NT) or gamma glutamyl transferasa (GGT) or alkaline phosphatase liver fraction should be performed, and if either of these is within normal limits (suggesting bone origin of abnormal alkaline phosphatase), patient may be included - AST, ALT < 2.5 x upper limit of normal - Albumin > 2.5 g/dl · Adequate renal function, with serum creatinine < 1.5 x ULN.
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E.4 | Principal exclusion criteria |
In Cohort A: . Small cell carcinoma of the prostate · Current treatment with chemotherapy or radiation therapy · Treatment with extensive external beam radiation therapy or radionuclide therapy within six weeks of study entry. Palliative radiation involving less than 20% of bone marrow reserves must have been completed within four weeks of entry · Treatment with chemotherapy within 4 weeks of study entry · Patient not employing adequate contraception · Other serious illness or medical conditions, specifically: - Uncontrolled congestive heart failure or HISTORY of myocardial infection or active angina pectoris within 6 months preceding registrations - Active infectious process - Chronic active liver disease, including chronic hepatitis B, chronic hepatitis C, or cirrhosis · Current anticancer treatment with any other non-FDA-approved investigational drug · ECOG performance status of 3 or worse
In Cohort B: · Small cell carcinoma of the prostate · Treatment with chemotherapy or radiation therapy was terminated at least 4 weeks before study entry · Treatment with extensive external beam radiation therapy or radionuclide therapy within six weeks of study entry. Palliative radiation involving less than 20% of bone marrow reserves must have been completed at least four weeks before study entry · Treatment with chemotherapy terminated at least 4 weeks before study entry · Patient not employing adequate contraception · Other serious illness or medical conditions, specifically: -Uncontrolled congestive heart failure or HISTORY of myocardial infection or active angina pectoris within 6 months preceding registrations - Active infectious process - Chronic active liver disease, including chronic hepatitis B, chronic hepatitis C, or cirrhosis · Current anticancer treatment with any other non-FDA-approved investigational drug · ECOG performance status of 3 or worse
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E.5 End points |
E.5.1 | Primary end point(s) |
PSA response, duration of response, and time to progression |
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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 | Information not present in EudraCT |
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) | 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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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Patients will be assessed for the endpoints of survival, serum PSA and toxicity. Based on these assessments, Yondelis® may be administered until progressive disease or until major toxicity occurs. |
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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 | |
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 | 2 |