Malignant Pleural MesotheliomaPhase 1/2MESO-02NCT01353482
A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma
A Phase 1/2 study testing Cisplatin, Pemetrexed and Vorinostat in people with Malignant Pleural Mesothelioma, run by University College, London.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Cisplatin, Pemetrexed and Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Cisplatin, Pemetrexed, Vorinostat, Placebo
- Keywords
- mesothelioma, vorinostat
- Medical subject headings
- Mesothelioma, Malignant, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles
PemetrexedDrug
Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles
VorinostatDrug
The dose and frequency of vorinostat will be determined in the Phase I study. Vorinostat will be given concurrently with Cisplatin/Pemetrexed.
PlaceboDrug
Patients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cisplatin; Drug: Pemetrexed; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I only - Dose-limiting toxicities
Measured: After 2 cycles of chemotherapy. (6 weeks after start of treatment)
Phase I only - Number of cycles of pemetrexed-cisplatin given
Measured: 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).
Measured: At progression or patient death.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2011 (estimated)
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Investigators
- Dean Fennell, Principal investigator, Queen's University of Belfast
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353482
- Sponsor's protocol ID
- UCL/08/0359
- Other IDs
- 2009-013638-26, 2009
- Acronym
- MESO-02
- Status last verified
- Mar 2012
- First submitted
- 11 May 2011
- Last updated
- 22 Mar 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT01353482
- Acronym / sponsor ID
- MESO-02 / UCL/08/0359
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- mesothelioma, vorinostat
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason 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.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- First posted
- 13 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase II only - Arm I | Active comparator | Drug: Cisplatin, Drug: Pemetrexed, Drug: VorinostatIf 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. |
| Phase II only - Arm 2 | Placebo comparator | Drug: Cisplatin, Drug: Pemetrexed, Drug: PlaceboIf 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CisplatinCisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles | Drug | Phase II only - Arm 2, Phase II only - Arm I |
| PemetrexedPatients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles | Drug | Phase II only - Arm 2, Phase II only - Arm I |
| VorinostatThe dose and frequency of vorinostat will be determined in the Phase I study. Vorinostat will be given concurrently with Cisplatin/Pemetrexed. | Drug | Phase II only - Arm I |
| PlaceboPatients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo. | Drug | Phase II only - Arm 2 |
Primary outcome
Phase I only - Dose-limiting toxicities
Time frame: 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).
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).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2012.
- Cancer Research UK and UCL Cancer Trials Centre (Coordinating Centre)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dean Fennell principal investigator
Queen's University of Belfast
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cisplatin, Pemetrexed and Vorinostat in people with Malignant Pleural Mesothelioma, run by University College, London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I only - Dose-limiting toxicities (time frame: After 2 cycles of chemotherapy. (6 weeks after start of treatment)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2012; AzTrials last refreshed its copy on 6 Nov 2026.