Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma
- Registration Number
- NCT06088290
- Lead Sponsor
- PharmaMar
- Brief Summary
The primary objective of this phase IIb/III study is to evaluate whether the combination of lurbinectedin plus doxorubicin given as first line treatment for metastatic leiomyosarcoma (LMS) prolongs the progression-free survival (PFS) by Independent Review Committee (IRC) when compared to doxorubicin administered as a single agent.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 360
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Participant signed and dated written informed consent of the patient obtained before any study-specific procedure.
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Age ≥ 18 years.
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Histologically confirmed diagnosis of metastatic LMS.
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Radiologically measurable disease according to the RECIST v.1.1.
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No previous systemic therapy for metastatic disease (i.e., first-line setting) and no previous anthracyclines. Note: prior chemotherapy (without anthracycline) in the context of adjuvant or neoadjuvant therapy is allowed.
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
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Adequate hematological, renal, metabolic and hepatic function:
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Hemoglobin ≥ 9.0 g/dL (patients may have received prior red blood cell [RBC] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and platelet count
≥ 100 x 109/L.
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
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Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is > ULN.
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Albumin ≥ 3.0 g/dL.
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Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
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Left ventricular ejection fraction (LVEF) > 50% assessed by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO).
-
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Wash-out periods:
- At least three weeks since last prior systemic treatment.
- At least three weeks since last prior major surgery and one week since last prior minor surgery.
- At least two weeks since last prior radiotherapy.
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Evidence of non-childbearing status for women of childbearing potential (WOCBP).
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Prior treatment with anthracyclines, lurbinectedin or trabectedin.
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Known low grade leiomyosarcoma (i.e., grade I).
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Known hypersensitivity to any of the components of the i.v. formulation of lurbinectedin or doxorubicin.
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Concomitant diseases/conditions:
- History of cardiac disease: myocardial infarction or unstable angina within the year prior to enrollment; or symptomatic or uncontrolled arrhythmia despite ongoing treatment.
- Patients with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
- Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
- Active uncontrolled infection.
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
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Use of strong or moderate inhibitors or strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin.
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Prior irradiation if only one target lesion (i.e., measurable) is available, unless progression of the lesion has been confirmed.
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Known myopathy.
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History of another neoplastic disease except for curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, properly treated carcinoma in situ of the uterine cervix or breast or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease within three years prior to randomization. In case of prior malignancy, theInvestigator should ensure, based on histology or clinical information, that the metastatic sites are sarcoma and not recurrence of the original malignancy.
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Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
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Women who are pregnant or breast feeding and fertile patients (men and women) who are not using a highly effective method of contraception.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase IIb (& Phase III if selected), Doxorubicin (dose A) + Lurbinectedin (dose B) Lurbinectedin Participants will receive doxorubicin and lurbinectedin intravenously every three weeks (q3wk) on day 1 of each treatment cycle (treatment cycle = three weeks). Phase IIb (& Phase III if selected), Doxorubicin (dose C) + Lurbinectedin (dose D) Lurbinectedin Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks). Phase IIb (& Phase III if selected), Doxorubicin (dose A) + Lurbinectedin (dose B) Doxorubicin Participants will receive doxorubicin and lurbinectedin intravenously every three weeks (q3wk) on day 1 of each treatment cycle (treatment cycle = three weeks). Phase IIb (& Phase III if selected), Doxorubicin (dose C) + Lurbinectedin (dose D) Doxorubicin Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks). Phase IIb & Phase III, Doxorubicin Doxorubicin Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks).
- Primary Outcome Measures
Name Time Method PFS by IRC Up to approximately 28 months
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 28 months Expression Levels of Molecular Biomarkers Associated with Response and/or Resistance to Treatment Up to approximately 28 months Overall Response Rate (ORR) by IRC and IA Up to approximately 28 months Duration of Response (DoR) by IRC and IA Up to approximately 28 months Clinical Benefit Rate (CBR) by IRC and IA Up to approximately 28 months PFS on Next-line Therapy (PFS2) by IA Up to approximately 28 months Number of Participants Experiencing Adverse Events (AE) Up to approximately 28 months Number of Participants Experiencing Severe Adverse Events (SAE) Up to approximately 28 months Change in Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Up to approximately 28 months Volume of Distribution of Lurbinectedin and Doxorubicin in the Plasma Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks) Number of Participants With Presence or Absence of Mutation per Molecular Biomarker Associated With Response and/or Resistance to Treatment Up to approximately 28 months PFS by Investigator's Assessment (IA) Up to approximately 28 months Clearance of Lurbinectedin and Doxorubicin in the Plasma Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
Trial Locations
- Locations (80)
Centre Eugène Marquis
🇫🇷Rennes Cedex, France
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Hospital - Phoenix
🇺🇸Phoenix, Arizona, United States
Precision NextGen Oncology
🇺🇸Beverly Hills, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sarcoma Oncology Center
🇺🇸Los Angeles, California, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Augusta University Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
🇺🇸Seattle, Washington, United States
Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin
🇦🇹Graz, Austria
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz
🇫🇷Besançon Cedex, Doubs, France
Institut de Cancérologie de l'Ouest - Angers
🇫🇷Angers cedex 02, Pays De La Loire, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, Provence Alpes Cote D-Azur, France
Centre Léon Bérard
🇫🇷Lyon, Rhone-Alpes, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre de Lutte contre le Cancer - Centre Oscar Lambret
🇫🇷Lille, France
Centre Hospitalier Universitaire Dupuytren 1
🇫🇷Limoges, France
Hôspital de la Timone
🇫🇷Marseille Cedex 5, France
Institut Curie
🇫🇷Paris, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau
🇫🇷Saint-Herblain, France
Gustave Roussy
🇫🇷Villejuif, France
LMU Klinikum - Campus Großhadern
🇩🇪München, Bayern, Germany
Helios Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Universitatsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitätsmedizin Mannheim
🇩🇪Manheim, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
🇮🇹Rozzano, Milan, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
🇮🇹Napoli, Naples, Italy
Centro di Riferimento Oncologico
🇮🇹Aviano, Italy
Istituto Ortopedico Rizzoli
🇮🇹Bologna, Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
🇮🇹Bologna, Italy
Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia
🇮🇹Candiolo, Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Istituto Oncologico Veneto - IRCCS
🇮🇹Padova, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Università Campus Bio-Medico di Roma
🇮🇹Roma, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Instituto Português de Oncologia do Porto Francisco Gentil
🇵🇹Porto, Portugal
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
🇪🇸Barcelona, Spain
Hospital Universitario de Canarias
🇪🇸La Laguna, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
START Madrid - CIOCC - HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Centre Hospitalier Universitaire Vaudois Lausanne
🇨🇭Lausanne, Switzerland
University Hospital Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Universitätsspital Basel
🇨🇭Basel, Switzerland
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom