Clinical trial NCT06088290: Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma
Official title: Randomized, Controlled, Open-label, Phase IIb/III Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Patients With Metastatic Leiomyosarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Leiomyosarcoma
Keywords: Leiomyosarcoma
Oncology
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2023-10-18
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Participant signed and dated written informed consent of the patient obtained before any study-specific procedure.
2. Age ≥ 18 years.
3. Histologically confirmed diagnosis of metastatic LMS.
4. Radiologically measurable disease according to the RECIST v.1.1.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
7. Adequate hematological, renal, metabolic and hepatic function:

   1. 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.
   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
   3. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is \> ULN.
   4. Albumin ≥ 3.0 g/dL.
   5. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
   6. Left ventricular ejection fraction (LVEF) \> 50% assessed by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO).
8. Wash-out periods:

   1. At least three weeks since last prior systemic treatment.
   2. At least three weeks since last prior major surgery and one week since last prior minor surgery.
   3. At least two weeks since last prior radiotherapy.
9. Evidence of non-childbearing status for women of childbearing potential (WOCBP).

Exclusion Criteria:

1. Prior treatment with anthracyclines, lurbinectedin or trabectedin.
2. Known low grade leiomyosarcoma (i.e., grade I).
3. Known hypersensitivity to any of the components of the i.v. formulation of lurbinectedin or doxorubicin.
4. Concomitant diseases/conditions:

   1. History of cardiac disease: myocardial infarction or unstable angina within the year prior to enrollment; or symptomatic or uncontrolled arrhythmia despite ongoing treatment.
   2. Patients with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
   3. 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.
   4. Active uncontrolled infection.
   5. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
5. Use of strong or moderate inhibitors or strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin.
6. Prior irradiation if only one target lesion (i.e., measurable) is available, unless progression of the lesion has been confirmed.
7. Known myopathy.
8. 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.
9. Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
10. Women who are pregnant or breast feeding and fertile patients (men and women) who are not using a highly effective method of contraception.

Primary outcomes:
measure: PFS by IRC
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 28 months
measure: PFS by Investigator's Assessment (IA)
timeFrame: Up to approximately 28 months
measure: Overall Response Rate (ORR) by IRC and IA
timeFrame: Up to approximately 28 months
measure: Duration of Response (DoR) by IRC and IA
timeFrame: Up to approximately 28 months
measure: Clinical Benefit Rate (CBR) by IRC and IA
timeFrame: Up to approximately 28 months
measure: PFS on Next-line Therapy (PFS2) by IA
timeFrame: Up to approximately 28 months
measure: Number of Participants Experiencing Adverse Events (AE)
timeFrame: Up to approximately 28 months
measure: Number of Participants Experiencing Severe Adverse Events (SAE)
timeFrame: Up to approximately 28 months
measure: Change in Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire
timeFrame: Up to approximately 28 months
measure: Clearance of Lurbinectedin and Doxorubicin in the Plasma
timeFrame: Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
measure: Volume of Distribution of Lurbinectedin and Doxorubicin in the Plasma
timeFrame: Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
measure: Number of Participants With Presence or Absence of Mutation per Molecular Biomarker Associated With Response and/or Resistance to Treatment
timeFrame: Up to approximately 28 months
measure: Expression Levels of Molecular Biomarkers Associated with Response and/or Resistance to Treatment
timeFrame: Up to approximately 28 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital - Phoenix
state: Arizona
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Sarcoma Oncology Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia Cancer Center
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
state: Washington
city: Graz
country: Austria
facility: Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Besançon Cedex
country: France
facility: Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz
state: Doubs
city: Angers cedex 02
country: France
facility: Institut de Cancérologie de l'Ouest - Angers
state: Pays De La Loire
city: Nice Cedex 2
country: France
facility: Centre Antoine Lacassagne
state: Provence Alpes Cote D-Azur
city: Lyon
country: France
facility: Centre Léon Bérard
state: Rhone-Alpes
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Centre de Lutte contre le Cancer - Centre Oscar Lambret
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Dupuytren 1
city: Marseille Cedex 5
country: France
facility: Hôspital de la Timone
city: Paris
country: France
facility: Institut Curie
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rennes Cedex
country: France
facility: Centre Eugène Marquis
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau
city: Villejuif
country: France
facility: Gustave Roussy
city: München
country: Germany
facility: LMU Klinikum - Campus Großhadern
state: Bayern
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus Dresden
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Manheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Rozzano
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
state: Milan
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
state: Naples
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
city: Candiolo
country: Italy
facility: Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia
city: Orbassano
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - IRCCS
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: START Madrid - CIOCC - HM Sanchinarro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
References: