Using Trabectedin for Advanced Mesenchymal Chondrosarcoma

Phase II Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

This study is testing if a drug called trabectedin can help people aged 16 and older with advanced mesenchymal chondrosarcoma that has gotten worse after previous treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: Italian Sarcoma Group (network)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Prato, Firenze and 6 other locations)
• Trial ID: NCT04305548 on ClinicalTrials.gov

What this trial studies

This phase II clinical study investigates the effectiveness of trabectedin in patients aged 16 and older who have progressive, advanced mesenchymal chondrosarcoma (MCS) with a specific genetic marker (HEY1-NCOA2 fusion). The study is multicenter and uncontrolled, focusing on patients who have previously undergone anthracycline-based chemotherapy. Participants must have measurable disease and evidence of progression within the last six months. The goal is to assess the activity of trabectedin in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are patients aged 16 and older with advanced mesenchymal chondrosarcoma who have the HEY1-NCOA2 fusion and have previously received anthracycline chemotherapy.

Not a fit: Patients with early-stage mesenchymal chondrosarcoma or those who have not been pre-treated with anthracycline-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced mesenchymal chondrosarcoma.

How similar studies have performed: While there have been studies on trabectedin for other sarcomas, this specific approach for HEY1-NCOA2 positive mesenchymal chondrosarcoma is novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 16 years old
2. Histological centrally confirmed diagnosis of skeletal or extra-skeletal MCS with the documented presence of HEY1-NCOA2 fusion
3. Locally advanced disease and/or metastatic disease
4. Measurable or evaluable disease with RECIST v1.1
5. Evidence of progression by RECIST v1.1 during the 6 months before study entry
6. Patients must be pre-treated with at least one prior chemotherapy treatment containing anthracyclines for the advanced phase of disease and with a maximum of 3 lines
7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
8. Adequate bone marrow function
9. Adequate organ function
10. Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
11. Cardiac ejection fraction ≥50% as measured by echocardiogram
12. No history of arterial and/or venous thromboembolic event within the previous 12 months
13. 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 and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.
14. Any other factors, that, at judgment of investigator, could affect the safety of the patients according to the available trabectedin safety data

Exclusion Criteria:

1. Other primary malignancy with \<5 years clinically assessed disease free interval, except basal cell skin cancer, cervical carcinoma in situ or other neoplasm judged to entail a low risk of relapse
2. Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered
3. Previous radiotherapy to 25% of the bone marrow
4. Major surgery within 2 weeks prior to study entry
5. Participation in another clinical study with an investigational product, which last dose was taken less than 4 weeks prior to the start of the treatment.
6. Persistent toxicities (≥ grade 2) with the exception of alopecia, caused by previous anticancer therapies.
7. Pregnancy or breast feeding
8. Grade III/IV cardiac problems as defined by the New York Heart Association Criteria
9. Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment
10. Known brain metastasis
11. Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis)
12. Known diagnosis oh human deficiency virus (HIV) infection
13. Active or chronic hepatitis B or C requiring treatment with antiviral therapy
14. Medical history of hemorrhage or a bleeding event ≥ Grade 3 within 4 weeks prior to the initiation of study treatment
15. Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results
16. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
17. Expected non-compliance to medical regimens

Where this trial is running

Prato, Firenze and 6 other locations

• Nuovo Ospedale di Prato — Prato, Firenze, Italy (RECRUITING)
• Policlinico Universitario Campus Biomedico — Roma, RM, Italy (NOT_YET_RECRUITING)
• Fondazione del Piemonte per l'Oncologia IRCC Candiolo — Candiolo, Torino, Italy (RECRUITING)
• Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors — Bologna, Italy (RECRUITING)
• Fondazione IRCSS Istituto Nazionale dei Tumori — Milan, Italy (RECRUITING)
• Ospedale Giaccone — Palermo, Italy (RECRUITING)
• Istituti Fisioterapici Ospitalieri - Ospedale Regina Elena — Roma, Italy (RECRUITING)

Study contacts

• Principal investigator: Silvia Stacchiotti, MD — Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
• Study coordinator: Silvia Stacchiotti, MD

Conditions: Mesenchymal Chondrosarcoma