E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Malignant Pleural Mesothelioma previously treated with systemic chemotherapy. |
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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 | 10035605 |
E.1.2 | Term | Pleural mesothelioma malignant advanced |
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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 prior chemotherapy that has included pemetrexed and either cisplatin or carboplatin 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 advance malignant mesothelioma who have failed prior chemotherapy that included pemetrexed and either cisplatin or carboplatin with respect to: (1) overall objective response rate; (2) progression-free-survival; (3) dyspnea score of lung cancer symptom scale modified for mesothelioma (LCSS-Meso) at Week 12; and (4) 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, which has progressed or relapsed following standard treatment which included pemetrexed and either cisplatin or carboplatin. The most recent regimen must have contained pemetrexed. b. Patients must have received prior therapy with pemetrexed and either cisplatin or carboplatin. No more than 2 prior systemic therapies are allowed and pemetrexed must have been part of the most recent regimen. c. Patient must have an area of pleural thickness measured by modified RECIST [13] that is at least 1.5 cm in diameter on a spiral computerized tomography (CT) scan. d. Patient has a Karnofsky performance scale status of ≥70 (see Appendix 1). e. Patient must have completed previous chemotherapy or radiotherapy at least 4 weeks before drug administration (6 weeks for nitrosoureas or mitomycin C) and have recovered from any treatment-related toxicities (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1 or recovered to pre-treatment levels).
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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. e. Patient has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival, defined as the time from randomization to the time of death from any cause. The number of patients with CTCAE Grade 3/4 will be used for the primary safety analysis.
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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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 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 | 5 |
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 | 5 |