A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma (MESO-02)

March 21, 2012 updated by: University College, London

Mesothelioma is a relatively rare cancer which is becoming more common. It can affect one of two areas; the pleura (the lining of the lung) or the peritoneum (the lining of the abdomen). Cancer affecting the pleura is the more common of these and is called Pleural Mesothelioma. This is most commonly caused by exposure to asbestos.

Unfortunately mesothelioma is usually diagnosed at an advanced stage and so treatment is based around controlling the disease and managing the symptoms, rather than curing the disease.

The standard treatment for Advanced Malignant Pleural Mesothelioma is a combination of two anticancer drugs; Pemetrexed and Cisplatin.

The trial will look into whether there are benefits of adding a third drug called Vorinostat to the treatment.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Mesothelioma is a rapidly lethal cancer which is increasing in incidence year on year. A projected doubling of cases has been predicted within the next two decades in Europe and the disease is usually diagnosed only after it has become advanced.

As yet the standard treatment for advanced mesothelioma, chemotherapy (cytotoxic drugs), is only for disease control and symptom management. A Phase I study of a drug called Vorinostat recently looked in to its effect, when given with standard cytotoxic drugs, on advanced solid tumours. The data for this study showed that this treatment caused a response in the tumours of patients with mesothelioma.

The study aims to examine the efficacy and safety of first-line vorinostat when used concurrently with cisplatin/pemetrexed.

In the proposed trial, we will initially conduct an initial run-in phase I study, to find the maximum tolerated dose, before embarking on the randomised phase II trial. The study is therefore in two stages:

Phase I study: to find the maximum tolerated dose of vorinostat in this patient group. Both safety (ie the observed number of Dose Limiting Toxicities per cohort and the overall toxicity profile) and the number of chemotherapy cycles administered will be used to determine the final dose of vorinostat to be used in the subsequent phase II study.

Randomised Phase II study: to evaluate the efficacy and safety of vorinostat (using the dose from the phase I study) versus placebo in combination with cisplatin and pemetrexed. The Phase II study will use a placebo and double-blinding to ensure that neither the patient nor the research team are aware of the allocated treatment, which should allow for accurate comparison of the two treatment arms and reduce the potential for researcher bias. Patients will be randomized 1:1 to the two treatment arms.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathological confirmation of malignant pleural mesothelioma
  • 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.
  • Performance status ECOG 01
  • Age > 18
  • Able to swallow oral medication
  • Adequate haematological status
  • Adequate organ function
  • 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.
  • Ability to understand and willing to sign the written informed consent to participate (including donation of diagnostic biopsy tissue for research).
  • Ability to comply with the requirements of the protocol

Exclusion Criteria:

  • Other investigational or commercial agents or therapies administered with the intent of treating the patient's malignancy.
  • Evidence of CNS metastases that in the opinion of the investigator should receive local treatment prior to systemic cytotoxic chemotherapy
  • Uncontrolled intercurrent illness
  • 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 nonmelanoma skin tumour or insitu cervix carcinoma.
  • 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 washout period
  • Preplanned surgery or procedures that would interfere with the conduct of the study.
  • Patients who have had surgery within 28 days of randomisation
  • Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrolment is not allowed. However, drain site radiotherapy is allowed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Phase II only - Arm I
If the patient is randomised into the Vorinostat arm they will be given Pemetrexed (500mg/m2 iv) and Cisplatin (75mg/m2 iv) on day one of a 21 day cycle plus the dose of Vorinostat determined in the phase I study.
Drug: Cisplatin
Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles
Drug: Pemetrexed
Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles
Drug: Vorinostat
The dose and frequency of vorinostat will be determined in the Phase I study. Vorinostat will be given concurrently with Cisplatin/Pemetrexed.
Placebo Comparator: Phase II only - Arm 2
If the patient is randomised into the placebo arm they will be given Pemetrexed (500mg/m2 iv) and Cisplatin (75mg/m2 iv) on day one of a 21 day cycle with the placebo for the same number of days as in the vorinostat arm.
Drug: Cisplatin
Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles
Drug: Pemetrexed
Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles
Drug: Placebo
Patients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I only - Dose-limiting toxicities
Time Frame: After 2 cycles of chemotherapy. (6 weeks after start of treatment)
After 2 cycles of chemotherapy. (6 weeks after start of treatment)
Phase I only - Number of cycles of pemetrexed-cisplatin given
Time Frame: After 2 cycles of chemotherapy (6 weeks after start of treatment).
After 2 cycles of chemotherapy (6 weeks after start of treatment).
Phase II only - Progression free survival
Time Frame: At progression or patient death.
Calculated as the time between the date of randomisation and date of first progression or death (from any cause), whichever occurs first. Patients who have not died or progressed will be censored at the date last seen alive (ie. the last assessment).
At progression or patient death.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Dean Fennell, Queen's University of Belfast

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

May 11, 2011

First Submitted That Met QC Criteria

May 12, 2011

First Posted (Estimate)

May 13, 2011

Study Record Updates

Last Update Posted (Estimate)

March 22, 2012

Last Update Submitted That Met QC Criteria

March 21, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL/08/0359
  • 2009-013638-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malignant Pleural Mesothelioma

Clinical Trials on Cisplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe