Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma.

July 13, 2021 updated by: Swiss Group for Clinical Cancer Research

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy, 15121
        • A.O. SS. Antonio e Biagio e Cesare Arrigo
      • Rozzano, Italy, 20089
        • Istituto Clinico Humanitas
  • Switzerland
      • Baden, Switzerland, 5404
        • Kantonsspital Baden
      • Bellinzona, Switzerland, 6500
        • IOSI Ospedale Regionale di Bellinzona e Valli
      • Chur, Switzerland, CH-7000
        • Kantonsspital Graubuenden
      • St. Gallen, Switzerland, 8401
        • Kantonsspital St.Gallen
      • Thun, Switzerland, 3600
        • Regionalspital Thun
      • Winterthur, Switzerland, CH-8401
        • Kantonsspital Winterthur

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lurbinectedin
Lurbinectedin 3.2 mg/m2 i.v. every 3 weeks (one cycle) until progression, unacceptable toxicity or patient's withdrawal.
Drug: Lurbinectedin
3.2 mg/m2 i.v. every 3 weeks
Other Names:
  • PM01183

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
at 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.

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.
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.

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.
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.
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.
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.
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.
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.

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.
From date of registration until the date of treatment discontinuation for any cause, assessed up to 30 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Study Chair: Miklos Pless, MD, Kantonsspital Winterthur KSW
  • Study Director: Yannis Metaxas, MD, Kantonsspital Graubünden, Chur
  • Study Chair: Roger von Moos, Prof, Kantonsspital Graubünden, Chur
  • Study Chair: Federica Grosso, MD, SS. Antonio e C. Arrigo Hospital Alessandria (Italy)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2017

Primary Completion (Actual)

June 11, 2021

Study Completion (Actual)

June 11, 2021

Study Registration Dates

First Submitted

July 4, 2017

First Submitted That Met QC Criteria

July 7, 2017

First Posted (Actual)

July 11, 2017

Study Record Updates

Last Update Posted (Actual)

July 14, 2021

Last Update Submitted That Met QC Criteria

July 13, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 17/16
  • 2017-001016-11 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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