E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027406 |
E.1.2 | Term | Mesothelioma |
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 compare the overall survival associated with vorinostat plus best supportive care versus that associated with placebo plus best supportive care for the treatment of patients with advanced malignant pleural mesothelioma who have failed at least one prior chemotherapy regimen, and to determine the overall safety and toxicity of vorinostat in this population. |
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E.2.2 | Secondary objectives of the trial |
To compare between vorinostat plus best supportive care versus placebo plus best supportive care for the treatment of patients with advanced malignant mesothelioma who have failed at least one prior chemotherapy regimen with respect to: a. Progression-free-survival b. Overall objective response rate c. Dyspnea score of lung cancer symptom scale modified for mesothelioma (LCSS-Meso) at Week 12; and d. Percent change from baseline in forced vital capacity (FVC) at Week 12.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Patient must have a histologically and/or cytologically confirmed diagnosis of epithelial, sarcomatoid, or mixed histology malignant pleural mesothelioma and: In countries where pemetrexed is an approved mesothelioma treatment, the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen with pemetrexed and either cisplatin or carboplatin. OR In countries where pemetrexed is not approved for mesothelioma, the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen. OR In the opinion of the investigator, pemetrexed is not the preferred therapy for the patient, and the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen. b. Patient must have received no more than 2 prior systemic therapy regimens. c. Patient must have an area of pleural rind thickness measured by meso-modified RECIST [10] that is at least 1.0 cm in line-length on a spiral computerized tomography (CT) scan.
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E.4 | Principal exclusion criteria |
a. Patient had prior treatment with an HDAC inhibitor (e.g., Depsipeptide, MS 275, LAQ-824, PXD-101, and valproic acid). Patients who have received such agents for other indications, e.g. epilepsy, may enroll on vorinostat trials after a 30-day washout period. b. Patient has an active infection for which the patient received intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drug. c. Patients with a "currently active" second malignancy other than non-melanoma skin cancers and carcinoma in situ of the cervix are not eligible. Patients are not considered to have a "currently active" second malignancy if they have completed therapy for the second malignancy and are disease free from prior malignancies for >5 years. d. Patient has uncontrolled brain metastases, e.g., previously treated brain metastases that is not stable in the last 6 weeks.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is overall survival. Survival is generally considered to be the best measurement of an oncology drug’s effectiveness. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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.8.5 | 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 | 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 | 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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The first interim analysis will occur after 50 patients have had 18 weeks of follow-up. The second interim analysis will occur after 220 patients have had 18 weeks of follow-up. The third interim analysis will occur after approximately 270 events have occurred. |
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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 | 26 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 26 |