A study which will identify the best dose of a new drug, Vorinostat, with standard chemotherapy and its effectiveness in treating malignant pleural mesothelioma.

• Conditions: Malignant pleural mesothelioma; MedDRA version: 14.0Level: PTClassification code 10059518Term: Pleural mesothelioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-013638-26-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: The secondary research questions for the Phase I study are; how safe is adding Vorinostat to the standard treatment and the disease response.;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;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.

Secondary Outcome Measures

Name	Time	Method
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;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.