Lurbinectedin Monotherapy in Patients With Progressive Malignant Pleural Mesothelioma.

NCT03213301 | Completed Phase 2 DMC

• 2 other identifiers: SAKK 17/162017-001016-11
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 8

Brief Summary

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

Conditions

Malignant Pleural Mesothelioma, Advanced

Keywords

Progressive Malignant Pleural Mesothelioma; Lurbinectedin; Mesothelioma; Phase II Trial

Outcome Measures

Primary Outcomes (1)

• 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).

  at 12 weeks

Secondary Outcomes (5)

• Progression-free survival (PFS)

  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)

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

• Disease control (DC) at 12 weeks

  at 12 weeks: From date of registration until 14 weeks after.

• Overall survival (OS)

  From date of registration until the date of death from any cause, assessed up to 30 months.

• Time to treatment failure (TTF)

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

Study Arms (1)

Lurbinectedin

EXPERIMENTAL

Lurbinectedin 3.2 mg/m2 i.v. every 3 weeks (one cycle) until progression, unacceptable toxicity or patient's withdrawal.

Drug: Lurbinectedin

Interventions

Lurbinectedin DRUG

3.2 mg/m2 i.v. every 3 weeks

Also known as: PM01183

Lurbinectedin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (8)

A.O. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, 15121, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

IOSI Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital St.Gallen

Sankt Gallen, 8401, Switzerland

Location

Regionalspital Thun

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8401, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 32085891 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Interventions

PM 01183

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yannis Metaxas, MD

  Kantonsspital Graubünden, Chur

  STUDY DIRECTOR

• 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)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective 2-stage single-arm open-label multicenter phase II trial.

Study Record Dates

• First Submitted: July 4, 2017
• First Posted: July 11, 2017
• Study Start: September 28, 2017
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: July 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); CH (6)