| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Malignant pleural mesothelioma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer of the lining of the lung |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059518 |
| E.1.2 | Term | Pleural mesothelioma malignant |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| The principal research question for the phase I study is to find the maximum tolerated dose of vorinostat, and use this with the number of chemotherapy cycles administered to determine the most appropriate dose of Vorinostat for the phase II trial. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary research questions for the Phase I study are; how safe is adding Vorinostat to the standard treatment and the disease response. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| MESO-02 Translational substudy v1.0 03/06/2011 DNA and RNA will be extracted using proprietary methods .A tissue microarray will be built (Queen’s University Tissue Core) enabling validation of predictive biomarkers determined from gene expression using immunohistochemistry and molecular genetic based validations. These biomarkers may be used in future studies. Blocks will be requested from the relevant pathology department by the treating clinician, who will also forward a copy of the patient’s consent form to the pathologist in order for the block to be sent to the central laboratory. |
|
| E.3 | Principal inclusion criteria |
| 1. Pathological confirmation of malignant pleural mesothelioma 2. Measurable disease using modified RECIST criteria with at least one lesion ≥ 1cm using spiral CT in a single dimension. This scan must be within 28 days of randomisation. 3. Performance status ECOG 0-1 4. Age > 18 5. Able to swallow oral medication 6. Adequate haematological status: a.Haemoglobin 10g/dl or greater. b.Neutrophil count 1.5 x 10*9/L or greater. c.Platelets 100 x 10*9/L or greater. 7. Adequate organ function: a.Bilirubin < 1.5x ULN, ALP < 2.5x ULN, ALT < 1.5x ULN b.creatinine < 1.5x ULN or calculated creatinine ≥ 50ml/min/1.73mg/m2 8. Negative serum or urine pregnancy test. Male subject agrees to use an acceptable method of birth control for the duration of the study and contraception must be used by women of child bearing potential. 9. Ability to understand and willing to sign the written informed consent to participate (including donation of diagnostic biopsy tissue for research). 10. Ability to comply with the requirements of the protocol |
|
| E.4 | Principal exclusion criteria |
| 1. Other investigational or commercial agents or therapies administered with the intent of treating the patient’s malignancy. 2. Evidence of CNS metastases that in the opinion of the investigator should receive local treatment prior to systemic cytotoxic chemotherapy 3. Uncontrolled intercurrent illness including but not limited to: a.Symptomatic neurological illness. b.Active uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment c.Uncontrolled or severe cardiovascular disease d. Significant pulmonary disease or hypoxia e. Psychiatric illness/social situations that would limit compliance with study requirements f. Human immunodeficiency virus (HIV)-positive patients; known hepatitis B or C infection g. Uncontrolled diabetes mellitus 4. The patient has a history of prior malignant tumour, unless the patient has been without evidence of disease for at least three years, or the tumour was a non-melanoma skin tumour or in-situ cervix carcinoma. 5. Pregnant women and women who are breast feeding 6. Prior exposure to vorinostat or another HDAC inhibitor is not allowed. Prior valproic acid is acceptable but only if there has been at least 30 days wash-out period 7. Pre-planned surgery or procedures that would interfere with the conduct of the study. 8. Patients who have had surgery within 28 days of randomisation should not be included 9. Receipt of extensive radiation therapy, systemic chemotherapy, or other anti-neoplastic therapy within 4 weeks before enrolment is not allowed. However, drain site radiotherapy is allowed. 10. Patients who have had a Yellow Fever vaccination within the previous 30 days. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| For the Phase I Study - the primary outcome measures are; • the number of patients with a dose limiting toxicity • the number of cycles of cisplatin/pemetrexed that patients complete |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| For the Phase I study • Dose limiting toxicities will be measured from start of treatment to the end of treatment. • The number of cycles of cisplatin/pemetrexed that a patient completes will be recorded as the patient receives treatment. |
|
| E.5.2 | Secondary end point(s) |
| In the Phase I study the Secondary end points are; • Toxicities, according to CTCAE grade (version 4); all grades and events will be examined • Tumour response; the number with a complete or partial response, stable disease, or disease progression |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| For the Phase I study • Toxicities and evidence of tumour response will be measured from start of treatment to 30 days after Day 30 of the last cycle of protocol treatment. |
|
| 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 | Yes |
| 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Information not present in EudraCT |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | 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
| 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 | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 0 |
| 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
|
| Completion of all trial procedures by participants (e.g. last follow−up visit). In the Phase I study this will be 30 days after day 30 of the last chemotherapy cycle received. |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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