Malignant Pleural Mesothelioma, AdvancedPhase 2NCT03213301
Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma.
A Phase 2 study testing Lurbinectedin in people with Malignant Pleural Mesothelioma, Advanced, run by Swiss Cancer Institute at 8 sites in 2 countries.
Trial summary
Aim of this study is to provide the "proof of concept" of efficacy and tolerability of lurbinectedin monotherapy in progressive malignant mesotheliomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma, Advanced
- What is being tested?
- Lurbinectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 28 Sep 2017to 11 Jun 2021
- Phase
- Phase 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
- Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
- Histologically confirmed malignant mesothelioma (all histologies are eligible)
- Progression on or after one line of platinum-based combination chemotherapy. Any previous treatment with surgery or radiotherapy is allowed
- ≤ 1 line of treatment with an immune checkpoint inhibitor
- Prior systemic treatment stopped at least 4 weeks before registration
- Measurable or evaluable disease according to the modified RECIST criteria for malignant pleural mesothelioma
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- Age ≥ 18 years
- ECOG performance status ≤ 1
- Adequate bone marrow function: hemoglobin ≥ 90 g/L; absolute neutrophil count ≥ 2 x 109/L, platelet count ≥ 100 x 109/L
- Adequate hepatic function: total bilirubin ≤ 1.5 ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN); aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN; albumin ≥ 30 g/L
- Adequate renal function: creatinine clearance ≥ 30 mL/min/1.73, calculated according to the corrected formula of Cockcroft-Gault
- Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and during 6 months thereafter. A negative pregnancy test before registration (within 7 days) into the trial is required for all women with child-bearing potential
- Men agree not to father a child during trial treatment and during 6 months after last treatment infusion.
Who cannot join
- Known brain or leptomeningeal metastases
- History of another hematologic or primary solid tumor (except for curatively treated basal or squamous cell carcinoma of the skin, properly treated in situ malignant melanoma, in situ carcinoma of the uterine cervix or pT1-2 prostate cancer with Gleason score ≤6) within five years prior to registration
- More than one previous line of chemotherapy. Re-challenge is not allowed
- Prior treatment with lurbinectedin or trabectedin
- Treatment with any other experimental drug within 4 weeks before registration
- Concomitant use of other anti-cancer drugs, anti-cancer surgical intervention or radiotherapy except for local pain control and/or other local symptoms (e.g. pleurodesis due to dyspnea)
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- Grade > 1 from any AE derived from previous treatment; alopecia any grade, grade ≤ 2 peripheral neuropathy and clinically not significant elevation of GGT grade ≤ 2 (according to the NCI-CTCAE v4.03) are allowed
- Treatment with cortisone (prednisolone > 10 mg or equivalent) for immune-mediated side effects from previous immunotherapy (if applicable)
- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
- Severe or uncontrolled endocrinopathy due to previous immune checkpoint inhibitor treatment (if applicable)
- Known history of human immunodeficiency virus or active chronic hepatitis C or hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antimicrobial treatment
- Known hypersensitivity to the trial drug or to any component of the trial drug
- Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Switzerland6 sites
Kantonsspital Baden
Baden, 5404
IOSI Ospedale Regionale di Bellinzona e Valli
Bellinzona, 6500
Kantonsspital Graubuenden
Chur, CH-7000
Kantonsspital St.Gallen
Sankt Gallen, 8401
Regionalspital Thun
Thun, 3600
Kantonsspital Winterthur
Winterthur, CH-8401
Italy2 sites
A.O. SS. Antonio e Biagio e Cesare Arrigo
Alessandria, 15121
Istituto Clinico Humanitas
Rozzano, 20089
About this study
Official title: Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma. A Multicenter, Single-arm Phase II Trial
Aim of this study is to provide the "proof of concept" of efficacy and tolerability of lurbinectedin monotherapy in progressive malignant mesotheliomas.
Read the detailed description
Malignant mesothelioma arises from the mesothelial cells of the pleural, peritoneal or pericardial lining and is often associated with asbestos exposition. There is no cure for most malignant mesotheliomas and the scope of all three major oncological therapeutic procedures (surgery, radiotherapy and chemotherapy) is to reduce/eliminate symptoms as well as to prolong progression free survival (PFS) and/or overall survival (OS). While progressive patients are still in good health able to undertake a second-line treatment, there is no standard treatment for progressive disease.
Lurbinectedin is a novel compound structurally related to trabectedin and with similar mode of action. Pre-clinical data showed a better safety profile than trabectedin. Lurbinectedin has been already tested in different Phase I-II trials showing promising activity in ovarian, pancreatic, breast, small and non-small cell lung cancer as well as in other tumor types, with objective responses averaging 30%, disease stabilization up to 75% and having manageable toxicity. Although lurbinectedin has not been widely tested in mesotheliomas, some mesothelioma patients have been already treated with lurbinectedin where again promising activity has been observed.
- Conditions
- Malignant Pleural Mesothelioma, Advanced
- Being tested
- Lurbinectedin
- Keywords
- Progressive Malignant Pleural Mesothelioma, Lurbinectedin, Mesothelioma, Phase II Trial
- 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.
LurbinectedinDrug
Also called PM01183
3.2 mg/m2 i.v. every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Lurbinectedin | Experimental | Lurbinectedin 3.2 mg/m2 i.v. every 3 weeks (one cycle) until progression, unacceptable toxicity or patient's withdrawal. Receives: Drug: Lurbinectedin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) at 12 weeks
PFS at 12 weeks is defined as absence of progression or death due to any cause during 12 weeks (±2 weeks) after registration.
Patients with no tumor assessment at 12 weeks (±2 weeks) will be considered:
- Progressed at 12 weeks, if they have no following tumor assessment within the trial (patient died, refused, started a new treatment or was lost to follow-up) or if they progress at the following tumor assessment after 12 weeks (±2 weeks).
- Progression-free at 12 weeks, if they do not progress at the following tumor assessment after 12 weeks (±2 weeks).
Measured: at 12 weeks
Secondary outcomes (5)
Progression-free survival (PFS)
PFS is defined as time from registration to one of the following events, whichever occurs first:
- Relapse or progression according to the modified RECIST criteria for malignant pleural mesothelioma
- Death due to any cause Patients not experiencing an event will be censored at the date of last evaluable tumor assessment before starting a subsequent treatment, if any.
Measured: From date of registration until the date of first documented relapse or progression according to the modified RECIST criteria for malignant pleural mesothelioma or date of death from any cause, whichever came first, assessed up to 30 months.
Objective response (OR)
OR is defined as complete response (CR) or partial response (PR) achieved by the patient during trial treatment. Tumor response will be evaluated according to the modified RECIST criteria for malignant pleural mesothelioma.
Patients without any tumor assessment during trial treatment will be regarded as having a non-evaluable response (NE) and shall be considered as failures for this endpoint.
Measured: From date of registration until the date of treatment discontinuation for any cause, assessed up to 30 months.
Disease control (DC) at 12 weeks
DC is defined as CR, PR or stable disease (SD) for at least 12 weeks achieved by the patient during trial treatment. Tumor response will be evaluated according to the modified RECIST criteria for malignant pleural mesothelioma.
Measured: at 12 weeks: From date of registration until 14 weeks after.
Overall survival (OS)
OS is defined as time from registration until death due to any cause. Patients alive or lost to follow-up will be censored at the last date they were known to be alive.
Measured: From date of registration until the date of death from any cause, assessed up to 30 months.
Time to treatment failure (TTF)
TTF is defined as time from registration until treatment discontinuation due to any reason (unacceptable toxicity, patient refusal, progression, death or any other event that determines the termination of the trial treatment).
Patients not experiencing an event will be censored at the date of their last available assessment or visit.
Measured: From date of registration until the date of treatment discontinuation for any cause, assessed up to 30 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start28 Sep 2017
- Primary completion11 Jun 2021
- Study completion11 Jun 2021
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 Malignant Pleural Mesothelioma, AdvancedStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective 2-stage single-arm open-label multicenter phase II trial.
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yannis Metaxas, MD, Study director, Kantonsspital Graubünden, ChurRoger von Moos, Prof, Study chair, Kantonsspital Graubünden, ChurMiklos Pless, MD, Study chair, Kantonsspital Winterthur KSWFederica Grosso, MD, Study chair, SS. Antonio e C. Arrigo Hospital Alessandria (Italy)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03213301
- Sponsor's protocol ID
- SAKK 17/16
- Other IDs
- 2017-001016-11, 2017
- Status last verified
- Jul 2021
- First submitted
- 4 Jul 2017
- Last updated
- 14 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Metaxas Y, Fruh M, Eboulet EI, Grosso F, Pless M, Zucali PA, Ceresoli GL, Mark M, Schneider M, Maconi A, Perrino M, Biaggi-Rudolf C, Froesch P, Schmid S, Waibel C, Appenzeller C, Rauch D, von Moos R; Swiss Group for Clinical Cancer Research (SAKK). Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16). Ann Oncol. 2020 Apr;31(4):495-500. doi: 10.1016/j.annonc.2019.12.009. Epub 2020 Jan 16.
PubMed 32085891
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma. A Multicenter, Single-arm Phase II Trial
- ClinicalTrials.gov ID
- NCT03213301
- Acronym / sponsor ID
- SAKK 17/16
- Conditions
- Malignant Pleural Mesothelioma, Advanced
- Keywords
- Progressive Malignant Pleural Mesothelioma, Lurbinectedin, Mesothelioma, Phase II Trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- 28 Sep 2017 (actual)
- Primary completion
- 11 Jun 2021 (actual)
- Study completion
- 11 Jun 2021 (actual)
- First posted
- 11 Jul 2017 (actual)
- 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.
Aim of this study is to provide the "proof of concept" of efficacy and tolerability of lurbinectedin monotherapy in progressive malignant mesotheliomas.
Detailed description
Malignant mesothelioma arises from the mesothelial cells of the pleural, peritoneal or pericardial lining and is often associated with asbestos exposition. There is no cure for most malignant mesotheliomas and the scope of all three major oncological therapeutic procedures (surgery, radiotherapy and chemotherapy) is to reduce/eliminate symptoms as well as to prolong progression free survival (PFS) and/or overall survival (OS). While progressive patients are still in good health able to undertake a second-line treatment, there is no standard treatment for progressive disease.
Lurbinectedin is a novel compound structurally related to trabectedin and with similar mode of action. Pre-clinical data showed a better safety profile than trabectedin. Lurbinectedin has been already tested in different Phase I-II trials showing promising activity in ovarian, pancreatic, breast, small and non-small cell lung cancer as well as in other tumor types, with objective responses averaging 30%, disease stabilization up to 75% and having manageable toxicity. Although lurbinectedin has not been widely tested in mesotheliomas, some mesothelioma patients have been already treated with lurbinectedin where again promising activity has been observed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective 2-stage single-arm open-label multicenter phase II trial.
| Arm | Type | Receives |
|---|---|---|
| Lurbinectedin | Experimental | Drug: LurbinectedinLurbinectedin 3.2 mg/m2 i.v. every 3 weeks (one cycle) until progression, unacceptable toxicity or patient's withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
- Histologically confirmed malignant mesothelioma (all histologies are eligible)
- Progression on or after one line of platinum-based combination chemotherapy. Any previous treatment with surgery or radiotherapy is allowed
- ≤ 1 line of treatment with an immune checkpoint inhibitor
- Prior systemic treatment stopped at least 4 weeks before registration
Key exclusion criteria (13 listed)
- Known brain or leptomeningeal metastases
- History of another hematologic or primary solid tumor (except for curatively treated basal or squamous cell carcinoma of the skin, properly treated in situ malignant melanoma, in situ carcinoma of the uterine cervix or pT1-2 prostate cancer with Gleason score ≤6) within five years prior to registration
- More than one previous line of chemotherapy. Re-challenge is not allowed
- Prior treatment with lurbinectedin or trabectedin
- Treatment with any other experimental drug within 4 weeks before registration
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 |
|---|---|---|
| LurbinectedinAlso: PM011833.2 mg/m2 i.v. every 3 weeks | Drug | Lurbinectedin |
Primary outcome
Progression free survival (PFS) at 12 weeks
Time frame: at 12 weeks
PFS at 12 weeks is defined as absence of progression or death due to any cause during 12 weeks (±2 weeks) after registration. Patients with no tumor assessment at 12 weeks (±2 weeks) will be considered: * Progressed at 12 weeks, if they have no following tumor assessment within the trial (patient died, refused, started a new treatment or was lost to follow-up) or if they progress at the following tumor assessment after 12 weeks (±2 weeks). * Progression-free at 12 weeks, if they do not progress at the following tumor assessment after 12 weeks (±2 weeks).
5 secondary outcomes
Progression-free survival (PFS)
Time frame: From date of registration until the date of first documented relapse or progression according to the modified RECIST criteria for malignant pleural mesothelioma or date of death from any cause, whichever came first, assessed up to 30 months.
Objective response (OR)
Time frame: From date of registration until the date of treatment discontinuation for any cause, assessed up to 30 months.
Disease control (DC) at 12 weeks
Time frame: at 12 weeks: From date of registration until 14 weeks after.
Overall survival (OS)
Time frame: From date of registration until the date of death from any cause, assessed up to 30 months.
Time to treatment failure (TTF)
Time frame: From date of registration until the date of treatment discontinuation for any cause, assessed up to 30 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 14 Jul 2021.
- Derived from this study: PubMed 32085891Metaxas Y, Fruh M, Eboulet EI, Grosso F, Pless M, Zucali PA, Ceresoli GL, Mark M, Schneider M, Maconi A, Perrino M, Biaggi-Rudolf C, Froesch P, Schmid S, Waibel C, Appenzeller C, Rauch D, von Moos R; Swiss Group for Clinical Cancer Research (SAKK). Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16). Ann Oncol. 2020 Apr;31(4):495-500. doi: 10.1016/j.annonc.2019.12.009. Epub 2020 Jan 16.
- Individual participant dataSharing planned: No
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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.
Yannis Metaxas, MD study director
Kantonsspital Graubünden, Chur
Roger von Moos, Prof study chair
Kantonsspital Graubünden, Chur
Miklos Pless, MD study chair
Kantonsspital Winterthur KSW
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lurbinectedin in people with Malignant Pleural Mesothelioma, Advanced, run by Swiss Cancer Institute at 8 sites in 2 countries.
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 13 inclusion and 13 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 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland, Italy. 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 phase mean?
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?
Progression free survival (PFS) at 12 weeks (time frame: at 12 weeks). 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 NCT03213301, 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 14 Jul 2021.