Brief Title
A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma
Official Title
A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Phase I only - Dose-limiting toxicities
Condition
Malignant Pleural Mesothelioma
Intervention
Cisplatin
Study Arms / Comparison Groups
Phase II only - Arm I
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
0
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Dean Fennell, ,
Administrative Informations
NCT ID
NCT01353482
Organization ID
UCL/08/0359
Secondary IDs
2009-013638-26
Study Sponsor
University College, London
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
Dean Fennell, Principal Investigator, Queen's University of Belfast
Verification Date
March 2012