Evaluating Trabectedin for Advanced Leiomyosarcoma

A Randomized Phase II Trial Comparing the Activity of trabectedIn vs Gemcitabine in Patients With Metastatic or Locally Advanced Leiomyosarcoma Pretreated With Conventional Chemotherapy

This study is testing if a drug called Trabectedin can help people with advanced leiomyosarcoma feel better and live longer compared to another treatment called Gemcitabine.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Italian Sarcoma Group (network)
• Drugs / interventions: chemotherapy, radiation
• Locations: 17 sites (Bologna, BO and 16 other locations)
• Trial ID: NCT04383119 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness of Trabectedin in patients with advanced leiomyosarcoma, comparing it to Gemcitabine. It includes a randomized cohort and an observational cohort for patients who cannot be randomized. The study will also conduct a translational research component to identify predictive factors for treatment response. The goal is to improve patient quality of life and potentially extend survival in a population with limited treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable or metastatic leiomyosarcoma who have previously received anthracycline-based chemotherapy.

Not a fit: Patients with resectable leiomyosarcoma or those who have not received prior systemic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced leiomyosarcoma.

How similar studies have performed: While Trabectedin has shown some activity in soft tissue sarcomas, this specific approach in leiomyosarcoma has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Patients with histologically documented diagnosis of leiomyosarcoma
2. Patients with diagnosis of unresectable or metastatic leiomyosarcoma
3. Patients who received at least on previous systemic treatment with anthracycline-based chemotherapy.
4. Patients suitable to receive gemcitabine or trabectedin therapy.
5. Measurable or evaluable disease with RECIST 1.1 criteria.
6. Evidence of progression according RECIST 1.1 during the 6 months before study entry.
7. Age ≥18 years
8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
9. All previous anticancer treatments must have completed ≥ 3 weeks prior to first dose of study drug.
10. The patient has resolution of adverse events, with the exception of alopecia, and of all clinically significant toxic effects of prior loco-regional therapy, surgery, radiotherapy or systemic anticancer therapy to ≤ Grade 1, by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
11. Adequate bone marrow, liver and renal function
12. Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of normality.
13. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
14. No history of arterial and/or venous thromboembolic event within the previous 12 months.
15. The patient or legal representative must be able to read and understand the informed consent form and must have been willing to give written informed consent prior to any study specific procedure. The subject may also provide an optional consent for the biological/translational sub-study associated.

Exclusion Criteria:

1. Prior treatment with Trabectedin and/or Gemcitabine
2. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse.
4. Persistent toxicities with the exception of alopecia, caused by previous anticancer therapies
5. Metastatic brain or meningeal tumors
6. Active viral hepatitis
7. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
8. Patients with any severe and/or uncontrolled medical conditions
9. Medical history of hemorrhage or a bleeding event ≥ Grade 3 (NCI-CTCAE v 5.0) within 4 weeks prior to the initiation of study treatment
10. Active clinically serious infections
11. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
12. Previous treatment with radiation therapy within 14 days of first day of study drug dosing,
13. Major surgery within 4 weeks prior to study entry
14. Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
15. Concomitant use of known strong or moderate CYP3A inducers
16. Patients undergoing renal dialysis or with Creatinin Clearance \<30 ml/min or Creatinine \>1,5 mg/dL
17. Pregnant or breast feeding patients
18. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol

Where this trial is running

Bologna, BO and 16 other locations

• Azienda Ospedaliera S. Orsola-Malpighi — Bologna, BO, Italy (RECRUITING)
• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST — Meldola, FC, Italy (RECRUITING)
• Nuovo Ospedale di Prato — Prato, Firenze, Italy (RECRUITING)
• Istituto Clinico Humanitas — Rozzano, MI, Italy (RECRUITING)
• Centro di Riferimento Oncologico di Aviano — Aviano, PD, Italy (NOT_YET_RECRUITING)
• Policlinico Universitario Campus Biomedico — Roma, RM, Italy (RECRUITING)
• IRCCS Fondazione Piemonte per l'Oncologia — Candiolo, Torino, Italy (RECRUITING)
• A.O.U.San Luigi Gonzaga — Orbassano, Torino, Italy (RECRUITING)
• Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors — Bologna, Italy (RECRUITING)
• H.San Martino di Genova — Genova, Italy (RECRUITING)
• Fondazione IRCCS INT Milano — Milan, Italy (NOT_YET_RECRUITING)
• Istituto Europeo di Oncologia — Milan, Italy (RECRUITING)
• IRCCS Istituto nazionale Tumori "Fondazione G.Pascale" — Naples, Italy (RECRUITING)
• Irccs Istituto Oncologico Veneto (Iov) — Padova, Italy (RECRUITING)
• Ospedale Giaccone — Palermo, Italy (RECRUITING)
• Istituto Regina Elena - IFO — Rome, Italy (RECRUITING)
• ASL Città di Torino (Dipartimento di Oncologia) — Torino, Italy (RECRUITING)

Study contacts

• Principal investigator: Bruno Vincenzi, Prof/MD — Campus Biomedico of Rome
• Study coordinator: Bruno Vincenzi, Prof/MD

Conditions: Leiomyosarcoma of Ovary, Soft Tissue Sarcoma, advanced leiomyosarcoma