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

Primary Purpose

Malignant Pleural Mesothelioma

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Cisplatin

Pemetrexed

Vorinostat

Placebo

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring mesothelioma, vorinostat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Phase II only - Arm I

Phase II only - Arm 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Phase I only - Dose-limiting toxicities

Phase I only - Number of cycles of pemetrexed-cisplatin given

Phase II only - Progression free survival

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT01353482

First Posted

May 11, 2011

Last Updated

March 21, 2012

Sponsor

University College, London

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01353482

Brief Title

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

Acronym

MESO-02

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Withdrawn

Why Stopped

UCL CTC were informed by Merck Sharp & Dohme on 22.08.11 that support for the trial had been withdrawn in light of results from another trial with trial drug.

Study Start Date

undefined (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

University College, London

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Pleural Mesothelioma

Keywords

mesothelioma, vorinostat

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase II only - Arm I

Arm Type

Active Comparator

Arm Description

Arm Title

Phase II only - Arm 2

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles

Intervention Type

Drug

Intervention Name(s)

Vorinostat

Intervention Description

The dose and frequency of vorinostat will be determined in the Phase I study. Vorinostat will be given concurrently with Cisplatin/Pemetrexed.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Patients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo.

Primary Outcome Measure Information:

Title

Phase I only - Dose-limiting toxicities

Time Frame

After 2 cycles of chemotherapy. (6 weeks after start of treatment)

Title

Phase I only - Number of cycles of pemetrexed-cisplatin given

Time Frame

After 2 cycles of chemotherapy (6 weeks after start of treatment).

Title

Phase II only - Progression free survival

Description

Time Frame

At progression or patient death.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dean Fennell

Organizational Affiliation

Queen's University of Belfast

Official's Role

Principal Investigator

12. IPD Sharing Statement

Links:

URL

http://www.ctc.ucl.ac.uk

Description

Cancer Research UK and UCL Cancer Trials Centre (Coordinating Centre)

Learn more about this trial

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

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