Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma

Leiomyosarcoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06088290
• Other study ID #: PM1183-C-010-22
• Secondary ID: 2022-502975-45
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 21, 2023
• Est. completion date: November 26, 2026

Study information

• Verified date: March 2024
• Source: PharmaMar
• Contact: Gaston Federico Boggio, M.D.
• Phone: +34 91 823 4524
• Email: gfboggio[@]pharmamar.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: November 26, 2026
• Est. primary completion date: November 26, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leiomyosarcoma

Intervention

Drug:
• Lurbinectedin
Intravenous Infusion
• Doxorubicin
Short intravenous push or bolus (according to label)

Locations

Country	Name	City	State
France	Institut de Cancérologie de l'Ouest - Angers	Angers cedex 02	Pays De La Loire
France	Institut Bergonié	Bordeaux
France	Centre de Lutte contre le Cancer - Centre Oscar Lambre	Lille
France	Centre Hospitalier Universitaire Dupuytren 1	Limoges
France	Centre Léon Bérard	Lyon	Rhone-Alpes
France	Hôspital de la Timone	Marseille Cedex 5
France	Centre Antoine Lacassagne	Nice Cedex 2	Provence Alpes Cote D-Azur
France	Institut de Cancérologie de l'Ouest - Saint-Herblain - Site René Gauducheau	Saint-Herblain
Germany	Universität Münster	Münster
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia	Candiolo
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Naples
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Account Istituto Nazionale Tumori Regina Elena	Roma
Italy	Università Campus Bio-Medico di Roma	Roma
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 Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	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	Hospital Universitario Miguel Servet	Zaragoza
United States	University of Michigan	Ann Arbor	Michigan
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	Sarcoma Oncology Center	Los Angeles	California
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS by IRC		Up to approximately 28 months
Secondary	PFS by Investigator's Assessment (IA)		Up to approximately 28 months
Secondary	Overall Response Rate (ORR) by IRC and IA		Up to approximately 28 months
Secondary	Duration of Response (DoR) by IRC and IA		Up to approximately 28 months
Secondary	Clinical Benefit Rate (CBR) by IRC and IA		Up to approximately 28 months
Secondary	PFS on Next-line Therapy (PFS2) by IA		Up to approximately 28 months
Secondary	Overall Survival (OS)		Up to approximately 28 months
Secondary	Number of Participants Experiencing Adverse Events (AE)		Up to approximately 28 months
Secondary	Number of Participants Experiencing Severe Adverse Events (SAE)		Up to approximately 28 months
Secondary	Change in Quality of Life by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire		Up to approximately 28 months
Secondary	Clearance of Lurbinectedin and Doxorubicin in the Plasma		Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
Secondary	Volume of Distribution of Lurbinectedin and Doxorubicin in the Plasma		Cycle 1 Day 1, and Day 5 (One cycle = 3 weeks)
Secondary	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
Secondary	Expression Levels of Molecular Biomarkers Associated with Response and/or Resistance to Treatment		Up to approximately 28 months