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Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma.

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ClinicalTrials.gov Identifier: NCT03213301
Recruitment Status : Active, not recruiting
First Posted : July 11, 2017
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief Summary:
Aim of this study is to provide the "proof of concept" of efficacy and tolerability of lurbinectedin monotherapy in progressive malignant mesotheliomas.

Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma, Advanced Drug: Lurbinectedin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective 2-stage single-arm open-label multicenter phase II trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma. A Multicenter, Single-arm Phase II Trial
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

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 Name: PM01183




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.

  4. 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.

  5. 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03213301


Locations
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Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy, 15121
Istituto Clinico Humanitas
Rozzano, Italy, 20089
Switzerland
Kantonsspital Baden
Baden, Switzerland, 5404
IOSI Ospedale Regionale di Bellinzona e Valli
Bellinzona, Switzerland, 6500
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Kantonsspital St.Gallen
St. Gallen, Switzerland, 8401
Regionalspital Thun
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8401
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
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Study Director: Yannis Metaxas, MD Kantonsspital Graubünden, Chur
Study Chair: Roger von Moos, Prof Kantonsspital Graubünden, Chur
Study Chair: Miklos Pless, MD Kantonsspital Winterthur KSW
Study Chair: Federica Grosso, MD SS. Antonio e C. Arrigo Hospital Alessandria (Italy)

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Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT03213301     History of Changes
Other Study ID Numbers: SAKK 17/16
2017-001016-11 ( EudraCT Number )
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Swiss Group for Clinical Cancer Research:
Progressive Malignant Pleural Mesothelioma
Lurbinectedin
Mesothelioma
Phase II Trial

Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial