Brief Title
Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma.
Official Title
Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma. A Multicenter, Single-arm Phase II Trial
Brief Summary
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression free survival (PFS) at 12 weeks
Secondary Outcome
Progression-free survival (PFS)
Condition
Malignant Pleural Mesothelioma, Advanced
Intervention
Lurbinectedin
Study Arms / Comparison Groups
Lurbinectedin
Description: Lurbinectedin 3.2 mg/m2 i.v. every 3 weeks (one cycle) until progression, unacceptable toxicity or patient's withdrawal.
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
42
Start Date
September 28, 2017
Completion Date
March 1, 2022
Primary Completion Date
April 8, 2019
Eligibility Criteria
Inclusion Criteria:
- 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
- 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.
Exclusion Criteria:
- 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)
- 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Yannis Metaxas, MD, ,
Location Countries
Italy
Location Countries
Italy
Administrative Informations
NCT ID
NCT03213301
Organization ID
SAKK 17/16
Secondary IDs
2017-001016-11
Responsible Party
Sponsor
Study Sponsor
Swiss Group for Clinical Cancer Research
Study Sponsor
Yannis Metaxas, MD, Study Director, Kantonsspital Graubünden, Chur
Verification Date
August 2020