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

NCT01353482 | Withdrawn Phase 1

• 2 other identifiers: UCL/08/03592009-013638-26
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Malignant Pleural Mesothelioma

Keywords

mesothelioma; vorinostat

Outcome Measures

Primary Outcomes (3)

• Phase I only - Dose-limiting toxicities

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

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

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

• 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).

  At progression or patient death.

Study Arms (2)

Phase II only - Arm I

ACTIVE COMPARATOR

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; Drug: Pemetrexed; Drug: Vorinostat

Phase II only - Arm 2

PLACEBO COMPARATOR

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; Drug: Pemetrexed; Drug: Placebo

Interventions

Cisplatin DRUG

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

Phase II only - Arm 2; Phase II only - Arm I

Pemetrexed DRUG

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

Phase II only - Arm 2; Phase II only - Arm I

Vorinostat DRUG

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

Phase II only - Arm I

Placebo DRUG

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

Phase II only - Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead
• Merck Sharp & Dohme LLC: collaborator

Related Links

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

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Interventions

Cisplatin; Pemetrexed; Vorinostat

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Dean Fennell

  Queen's University of Belfast

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: May 13, 2011
• Last Updated: March 22, 2012

Record last verified: 2012-03