Lung Cancer - Malignant Pleural MesotheliomaPhase 1/2MESO-02NCT01590160
Ganetespib With Platinum, in Patients With Malignant Pleural Mesothelioma
A Phase 1/2 study testing Ganetespib in people with Lung Cancer - Malignant Pleural Mesothelioma, run by University College, London at 1 site in United Kingdom.
Trial summary
Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos. Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer - Malignant Pleural Mesothelioma
- What is being tested?
- Ganetespib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2013to 5 Nov 2019
- 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
- Histopathological confirmation of malignant pleural mesothelioma
- Measurable disease using meso-modified RECIST criteria (CT scan must be within 28 days of registration/randomisation)
- Performance status ECOG 0-1
- Age at least 18 years
- Adequate haematological status:
- Haemoglobin 100g/L or greater
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- Neutrophil count ≥2.0 x 10^9/L
- Platelets ≥100 x 10^9 /L
- Adequate organ function:
- Bilirubin ≤1.5x ULN, ALP ≤2.5x ULN, ALT or AST ≤1.5x ULN
- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60ml/min (C\&G or EDTA)
- Chemotherapy naïve
- Negative serum pregnancy test for female patients of child bearing potential.
- Male subjects and women of child bearing potential must agree to use an acceptable method of birth control for the duration of the trial and for 6 months after the last trial treatment cycle has finished.
- 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
- Prior exposure to other investigational or commercial agents or therapies administered with the intent of treating the patient's malignancy. This includes crizotinib, other ALK-targeted agents, and any Hsp90 inhibitor (e.g. ganetespib). Prior valproic acid is acceptable but only if there has been at least 30 days wash-out period
- Evidence of CNS metastases that in the opinion of the investigator should receive local treatment prior to systemic cytotoxic chemotherapy
- Uncontrolled intercurrent illness including but not limited to:
- Symptomatic neurological illness
- Active uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment
- Significant pulmonary disease or hypoxia
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- Psychiatric illness/social situations that would limit compliance with trial requirements
- Human immunodeficiency virus (HIV)-positive patients
- Known hepatitis B or C infection
- Uncontrolled diabetes mellitus
- Serum potassium, magnesium, and calcium levels no more than 10% outside the Sites normal reference ranges
- Known serious cardiac illness including but not confined to:
- Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
- Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia anti-arrhythmic drug (e.g., quinidine, procainamide, disopyramide) or Class III anti-arrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other anti-arrhythmic drugs is permitted.
- Use of medications that have been linked to the occurrence of torsades de pointes
- Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker
- Complete left bundle branch block (LBBB)
- History of long QT Syndrome or a family member with this condition
- QTc >470ms (average of triplicate ECG recordings); a consistent method of QTc calculation must be used for each patient's QTc measurements. QTcF (Fridericia's formula) is preferred
- 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 non-melanoma skin tumour or in situ cervix carcinoma
- Pregnant women or those who are lactating
- Pre-planned surgery or procedures that would interfere with the conduct of the trial
- Patients who have had surgery (does not include pleurodesis or pleurectomy) within 28 days of randomisation should not be included
- Previous treatment of mesothelioma with systemic chemotherapy
- Receipt of extensive radiation therapy, systemic chemotherapy, or other anti-neoplastic therapy within 4 weeks before enrolment is not allowed. However, drain site radiotherapy is allowed
- Significant weight loss (≥10% body weight) within the 4 weeks prior to Cycle 1 Day 1.
- Patients who have had a yellow fever vaccination in the previous 30 days.
- Other medications, severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of First Line Ganetespib With Platinum, in Patients With Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos.
Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. MPM is characterized by local invasion of adjacent structures including the chest wall, mediastinum, diaphragm and pericardium resulting in progressive shortness of breath.
Median survival with best supportive care alone is approximately 6-9 months and most cases of mesothelioma present in the advanced setting. Therefore this trial will be looking at whether a new drug, Ganetespib has any improvement on survival for these types of patients.
- Being tested
- Ganetespib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanetespibDrug
IV, Using dose from Phase I
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin/Pemetrexed | Experimental | Cisplatin 75mg/m2, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days Receives: Drug: Ganetespib |
| Carboplatin/Pemetrexed | Experimental | Carboplatin AUC5, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days Receives: Drug: Ganetespib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Ganetespib
Primary endpoint (phase I): Dose-limiting toxicities during Cycles 1 \& 2; and number of cycles of pemetrexed-cisplatin given.
The Phase I trial will consist of three ganetespib dose cohorts, each with 3 or 6 patients:
- Cohort 1: 100mg/m2 IV on day 1 and day 15 of each cycle
- Cohort 2: 150mg/m2 IV on day 1 and day 15 of each cycle
- Cohort 3: 200mg/m2 IV on day 1 and day 15 of each cycle
There will be additional patients to be treated with carboplatin (AUC5) instead of cisplatin. If treatment with carboplatin is confirmed to be safe and tolerable, the option of treating patients with either cisplatin or carboplatin during phase II will be taken. The evaluation will be done using an accelerated titrated phase I design.
Primary endpoint (phase II): Progression free survival
Measured: 6 Months
Secondary outcomes (1)
Progression Free Survival
Secondary endpoints (phase I):
- To examine the number of cycles of pemetrexed/platinum chemotherapy administered.
- To examine the objective tumour response according to meso-modified RECIST, and the overall response rate.
Secondary endpoints (phase II):
- To examine the frequency of all Adverse Events graded by NCI-CTCAE version 4, in particular those with grade 3 or 4 events.
- To examine the objective tumour response according to meso-modified RECIST, and the overall response rate.
- To examine overall survival.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2012 (estimated)
- Study startAug 2013
- Primary completion5 Nov 2019
- Study completion5 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung Cancer - 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
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Professor D Fennell, MBBS, Study chair, University of Leicester & Leicester University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01590160
- Sponsor's protocol ID
- UCL/12/0158
- Other IDs
- CMS # 1995, A15183, 2012-001598-10
- Acronym
- MESO-02
- Status last verified
- Nov 2019
- First submitted
- 30 Apr 2012
- Last updated
- 13 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fennell DA, Danson S, Woll PJ, Forster M, Talbot D, Child J, Farrelly L, Sharkey A, Busacca S, Ngai Y, Hackshaw A, Wheeler GM. Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial. Clin Cancer Res. 2020 Sep 15;26(18):4748-4755. doi: 10.1158/1078-0432.CCR-20-1306. Epub 2020 Jul 15.
PubMed 32669375
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of First Line Ganetespib With Platinum, in Patients With Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT01590160
- Acronym / sponsor ID
- MESO-02 / UCL/12/0158
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Cancer Research UK
- Study start
- Aug 2013 (actual)
- Primary completion
- 5 Nov 2019 (actual)
- Study completion
- 5 Nov 2019 (actual)
- First posted
- 2 May 2012 (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.
Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos.
Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. MPM is characterized by local invasion of adjacent structures including the chest wall, mediastinum, diaphragm and pericardium resulting in progressive shortness of breath.
Median survival with best supportive care alone is approximately 6-9 months and most cases of mesothelioma present in the advanced setting. Therefore this trial will be looking at whether a new drug, Ganetespib has any improvement on survival for these types of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cisplatin/Pemetrexed | Experimental | Drug: GanetespibCisplatin 75mg/m2, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days |
| Carboplatin/Pemetrexed | Experimental | Drug: GanetespibCarboplatin AUC5, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histopathological confirmation of malignant pleural mesothelioma
- Measurable disease using meso-modified RECIST criteria (CT scan must be within 28 days of registration/randomisation)
- Performance status ECOG 0-1
- Age at least 18 years
- Adequate haematological status:
Key exclusion criteria (28 listed)
- Prior exposure to other investigational or commercial agents or therapies administered with the intent of treating the patient's malignancy. This includes crizotinib, other ALK-targeted agents, and any Hsp90 inhibitor (e.g. ganetespib). Prior valproic acid is acceptable but only if there has been at least 30 days wash-out period
- Evidence of CNS metastases that in the opinion of the investigator should receive local treatment prior to systemic cytotoxic chemotherapy
- Uncontrolled intercurrent illness including but not limited to:
- Serum potassium, magnesium, and calcium levels no more than 10% outside the Sites normal reference ranges
- Known serious cardiac illness including but not confined to:
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 |
|---|---|---|
| GanetespibIV, Using dose from Phase I | Drug | Carboplatin/Pemetrexed, Cisplatin/Pemetrexed |
Primary outcome
Maximum Tolerated Dose of Ganetespib
Time frame: 6 Months
Primary endpoint (phase I): Dose-limiting toxicities during Cycles 1 \& 2; and number of cycles of pemetrexed-cisplatin given. The Phase I trial will consist of three ganetespib dose cohorts, each with 3 or 6 patients: * Cohort 1: 100mg/m2 IV on day 1 and day 15 of each cycle * Cohort 2: 150mg/m2 IV on day 1 and day 15 of each cycle * Cohort 3: 200mg/m2 IV on day 1 and day 15 of each cycle There will be additional patients to be treated with carboplatin (AUC5) instead of cisplatin. If treatment with carboplatin is confirmed to be safe and tolerable, the option of treating patients with either cisplatin or carboplatin during phase II will be taken. The evaluation will be done using an accelerated titrated phase I design. Primary endpoint (phase II): Progression free survival
1 secondary outcome
Progression Free Survival
Time frame: 24 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Derived from this study: PubMed 32669375Fennell DA, Danson S, Woll PJ, Forster M, Talbot D, Child J, Farrelly L, Sharkey A, Busacca S, Ngai Y, Hackshaw A, Wheeler GM. Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial. Clin Cancer Res. 2020 Sep 15;26(18):4748-4755. doi: 10.1158/1078-0432.CCR-20-1306. Epub 2020 Jul 15.
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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.
Professor D Fennell, MBBS study chair
University of Leicester & Leicester University Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ganetespib in people with Lung Cancer - Malignant Pleural Mesothelioma, run by University College, London at 1 site in United Kingdom.
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 16 inclusion and 28 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: finished, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose of Ganetespib (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01590160, which also lists 1 linked publication.
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 13 Nov 2019.