Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

Phase 2

Recruiting

• Conditions: Mesenchymal Chondrosarcoma
• Interventions: Drug: Trabectedin

• Registration Number: NCT04305548
• Lead Sponsor: Italian Sarcoma Group

Brief Summary

Prospective, uncontrolled, investigator-initiated, phase II clinical study to explore the activity of trabectedin in a population of patients aged ≥16 years with progressive, advanced (locally advanced or metastatic)

Detailed Description

Prospective, uncontrolled, multicenter, Italian, investigator-initiated, phase II clinical study to explore the activity of trabectedin in a population of patients aged ≥16 years with progressive, advanced (locally advanced or metastatic), HEY1-NCOA2 positive MCS) , pre-treated with anthracycline-based chemotherapy.

Study Timeline

• Study First Submitted: 2020-03-09
• Study First Submitted QC: 2020-03-11
• Study First Posted: 2020-03-12
• Study Start: 2021-09-14
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-20
• Primary Completion: 2025-08-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trabectedin	Trabectedin	Trabectedin: 1.5 mg/m² - 1.3 mg/m² (at investigator's discretion, with a top-dose of 2.6 total mg per cycle), given in 24-hour continuous infusion

Primary Outcome Measures

Name	Time	Method
Overall tumour Response Rate, according to RECIST v 1.	At weeks 6	Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	At 3 and 5 years	Survival without disease progression
Choi criteria response rate	At weeks 6, 12,18, 30, 42	Response rate according Choi criteria
Clinical Benefit Rate	Month 6	Proportion of patient alive, without disease progression, after 6 months of treatment.
Adverse events related to the treatment	Week 3, week 6, week 9, week 12, week 18, week 24, week 36, week 48, week 60, week 72	Safety in term of grading of adverse event is evaluate from the first treatment dose throughout the study according to CTCAE 5.0
Overall Survival	At 3 and 5 years	Proportion of patients who are still alive at 36 and 60 months after have started the treatment
Duration of response	At weeks 6, 12,18, 30, 42	Duration of time between the date of first documented response and the date of first documented progression or death due to any cause

Trial Locations

Locations (7)

Nuovo Ospedale di Prato; 🇮🇹 Prato, Firenze, Italy

Policlinico Universitario Campus Biomedico; 🇮🇹 Roma, RM, Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo; 🇮🇹 Candiolo, Torino, Italy

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors; 🇮🇹 Bologna, Italy

Fondazione IRCSS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy

Istituti Fisioterapici Ospitalieri - Ospedale Regina Elena; 🇮🇹 Roma, Italy

Ospedale Giaccone; 🇮🇹 Palermo, Italy