RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The primary objective of this phase 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.

Official Title

Randomized, Controlled, Open-label, Phase III Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Patients With Metastatic Leiomyosarcoma

Quick Facts

Study Start:2023-09-21

Study Completion:2029-08-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06088290

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Voluntary signed and dated written informed consent of the participants obtained before any study-specific procedure. 2. Age ≥ 18 years. 3. Histologically confirmed diagnosis of metastatic LMS, in participants not candidates for curative resection. 4. Radiologically measurable disease according to the Response Evaluation Criteria in Solid Tumors (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. Prior line/s of hormone therapy in the adjuvant/metastatic setting are also 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 (participants may have received prior red blood cell \[Red Blood Cell\] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10\^9/L, and platelet count 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) or cardiac magnetic resonance imaging (MRI). 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 (port placement is excluded from this wash-out period). 3. At least two weeks since last prior radiotherapy. 9. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to seven months after treatment discontinuation. Fertile male participants with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.	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 IV formulation of lurbinectedin or doxorubicin. 4. Concomitant diseases/conditions: 1. History of cardiac disease: myocardial infarction or angina within the year prior to enrollment; severe vascular disease; or symptomatic arrhythmia despite ongoing treatment. 2. Participants 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 (including severe cardiovascular disease) or risk factors that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study. 5. Use of strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin. 6. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is available, unless progression of the lesion has been confirmed. 7. Known myopathy (history of resolved steroid-induced myopathy is allowed). 8. History of malignancies other than LMS within three years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior malignancies should have received curative treatment and should remain in remission. The Investigator should ensure, based on histology or clinical information, that the current metastatic sites are leiomyosarcoma and not recurrence of the original malignancy. 9. Limitation of the participant's ability to comply with the treatment or to follow-up the protocol. 10. Women who are pregnant or breast feeding and fertile participants (men and women) who are not using a highly effective method of contraception. 11. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to a critical structure).

Inclusion Criteria

Exclusion Criteria

1. Voluntary signed and dated written informed consent of the participants obtained before any study-specific procedure.
2. Age ≥ 18 years.
3. Histologically confirmed diagnosis of metastatic LMS, in participants not candidates for curative resection.
4. Radiologically measurable disease according to the Response Evaluation Criteria in Solid Tumors (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. Prior line/s of hormone therapy in the adjuvant/metastatic setting are also 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 (participants may have received prior red blood cell \[Red Blood Cell\] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10\^9/L, and platelet count
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) or cardiac magnetic resonance imaging (MRI).
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 (port placement is excluded from this wash-out period).
3. At least two weeks since last prior radiotherapy.
9. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to seven months after treatment discontinuation. Fertile male participants with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.

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 IV formulation of lurbinectedin or doxorubicin.
4. Concomitant diseases/conditions:
1. History of cardiac disease: myocardial infarction or angina within the year prior to enrollment; severe vascular disease; or symptomatic arrhythmia despite ongoing treatment.
2. Participants 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 (including severe cardiovascular disease) or risk factors that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
5. Use of strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin.
6. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is available, unless progression of the lesion has been confirmed.
7. Known myopathy (history of resolved steroid-induced myopathy is allowed).
8. History of malignancies other than LMS within three years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior malignancies should have received curative treatment and should remain in remission. The Investigator should ensure, based on histology or clinical information, that the current metastatic sites are leiomyosarcoma and not recurrence of the original malignancy.
9. Limitation of the participant's ability to comply with the treatment or to follow-up the protocol.
10. Women who are pregnant or breast feeding and fertile participants (men and women) who are not using a highly effective method of contraception.
11. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to a critical structure).

Contacts and Locations

Study Contact

Gaston Federico Boggio, M.D.

CONTACT

+34 91 823 4524

gfboggio@pharmamar.com

Study Locations (Sites)

Mayo Clinic Hospital - Phoenix

Phoenix, Arizona, 85054

United States

Precision NextGen Oncology

Beverly Hills, California, 90212

United States

Cedars-Sinai Medical Center

Los Angeles, California, 90025

United States

Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

Sarcoma Oncology Center

Los Angeles, California, 90057

United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224

United States

Augusta University Georgia Cancer Center

Augusta, Georgia, 30912

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

United States

Washington University School of Medicine in St. Louis

Saint Louis, Missouri, 63110

United States

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232

United States

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: PharmaMar

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-21

Study Completion Date2029-08-30

Study Record Updates

Study Start Date2023-09-21

Study Completion Date2029-08-30

Terms related to this study

Keywords Provided by Researchers

Leiomyosarcoma
Oncology

Additional Relevant MeSH Terms

Leiomyosarcoma