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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Withdrawn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
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

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

    First Posted
    May 11, 2011
    Last Updated
    March 21, 2012
    Sponsor
    University College, London
    Collaborators
    Merck Sharp & Dohme LLC
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    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
    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.
    Arm Title
    Phase II only - Arm 2
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    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
    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).
    Time Frame
    At progression or patient death.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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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