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

• ClinicalTrials.gov Identifier: NCT06088290
• Recruitment Status: Recruiting
• First Posted: October 18, 2023
• Last Update Posted: April 29, 2024
• Sponsor: PharmaMar
• Information provided by (Responsible Party): PharmaMar

Tracking Information

• First Submitted Date: September 28, 2023
• First Posted Date: October 18, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: September 21, 2023
• Estimated Primary Completion Date: November 26, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 16, 2023): PFS by IRC [ Time Frame: Up to approximately 28 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 16, 2023)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Leiomyosarcoma

Intervention

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

Study Arms

• Experimental: Phase IIb (& Phase III if selected), Doxorubicin (dose A) + Lurbinectedin (dose B)
  Participants will receive doxorubicin and lurbinectedin intravenously every three weeks (q3wk) on day 1 of each treatment cycle (treatment cycle = three weeks).
  Interventions:

  • Drug: Lurbinectedin
  • Drug: Doxorubicin
• Experimental: Phase IIb (& Phase III if selected), Doxorubicin (dose C) + Lurbinectedin (dose D)
  Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks).
  Interventions:

  • Drug: Lurbinectedin
  • Drug: Doxorubicin
• Active Comparator: Phase IIb & Phase III, Doxorubicin
  Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks).
  Intervention: Drug: Doxorubicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 16, 2023): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 26, 2026
• Estimated Primary Completion Date: November 26, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gaston Federico Boggio, M.D.; +34 91 823 4524; gfboggio@pharmamar.com

• Listed Location Countries: France, Germany, Italy, Spain, United States

Administrative Information

• NCT Number: NCT06088290
• Other Study ID Numbers: PM1183-C-010-22; 2022-502975-45 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: PharmaMar
• Original Responsible Party: Same as current
• Current Study Sponsor: PharmaMar
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PharmaMar
• Verification Date: March 2024