Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

NCT04305548 | Recruiting Phase 2

• 1 other identifier: ISG-MCS
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

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)

Conditions

Mesenchymal Chondrosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall tumour Response Rate, according to RECIST v 1.

  Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  At weeks 6

Secondary Outcomes (6)

• Choi criteria response rate

  At weeks 6, 12,18, 30, 42

• Overall Survival

  At 3 and 5 years

• Progression Free Survival (PFS)

  At 3 and 5 years

• Clinical Benefit Rate

  Month 6

• Duration of response

  At weeks 6, 12,18, 30, 42

Study Arms (1)

Trabectedin

EXPERIMENTAL

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

Drug: Trabectedin

Interventions

Trabectedin DRUG

Treatment with 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

Trabectedin

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 16 years old
• Histological centrally confirmed diagnosis of skeletal or extra-skeletal MCS with the documented presence of HEY1-NCOA2 fusion
• Locally advanced disease and/or metastatic disease
• Measurable or evaluable disease with RECIST v1.1
• Evidence of progression by RECIST v1.1 during the 6 months before study entry
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Adequate bone marrow function
• Adequate organ function
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
• Cardiac ejection fraction ≥50% as measured by echocardiogram
• No history of arterial and/or venous thromboembolic event within the previous 12 months
• 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.
• Any other factors, that, at judgment of investigator, could affect the safety of the patients according to the available trabectedin safety data

You may not qualify if:

• 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
• 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
• Previous radiotherapy to 25% of the bone marrow
• Major surgery within 2 weeks prior to study entry
• 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.
• Persistent toxicities (≥ grade 2) with the exception of alopecia, caused by previous anticancer therapies.
• Pregnancy or breast feeding
• Grade III/IV cardiac problems as defined by the New York Heart Association Criteria
• 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
• Known brain metastasis
• Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis)
• Known diagnosis oh human deficiency virus (HIV) infection
• Active or chronic hepatitis B or C requiring treatment with antiviral therapy
• Medical history of hemorrhage or a bleeding event ≥ Grade 3 within 4 weeks prior to the initiation of study treatment
• 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

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• PharmaMar: collaborator

Study Sites (7)

Nuovo Ospedale di Prato

Prato, Firenze, 59100, Italy

RECRUITING

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

NOT YET RECRUITING

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

RECRUITING

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, 40136, Italy

RECRUITING

Fondazione IRCSS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Ospedale Giaccone

Palermo, Italy

RECRUITING

Istituti Fisioterapici Ospitalieri - Ospedale Regina Elena

Roma, 00128, Italy

RECRUITING

Related Publications (5)

• Lee AF, Hayes MM, Lebrun D, Espinosa I, Nielsen GP, Rosenberg AE, Lee CH. FLI-1 distinguishes Ewing sarcoma from small cell osteosarcoma and mesenchymal chondrosarcoma. Appl Immunohistochem Mol Morphol. 2011 May;19(3):233-8. doi: 10.1097/PAI.0b013e3181fd6697.

  PMID: 21084965 BACKGROUND

• Wang L, Motoi T, Khanin R, Olshen A, Mertens F, Bridge J, Dal Cin P, Antonescu CR, Singer S, Hameed M, Bovee JV, Hogendoorn PC, Socci N, Ladanyi M. Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer. 2012 Feb;51(2):127-39. doi: 10.1002/gcc.20937. Epub 2011 Oct 27.

  PMID: 22034177 BACKGROUND

• Morioka H, Takahashi S, Araki N, Sugiura H, Ueda T, Takahashi M, Yonemoto T, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Susa M, Nakayama R, Nishimoto K, Kikuta K, Horiuchi K, Kawai A. Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma. BMC Cancer. 2016 Jul 14;16:479. doi: 10.1186/s12885-016-2511-y.

  PMID: 27418251 BACKGROUND

• Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, Erba E, Grosso F, Gronchi A, Aman P, Casali P, D'Incalci M, Pilotti S, Mantovani R. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther. 2009 Feb;8(2):449-57. doi: 10.1158/1535-7163.MCT-08-0848. Epub 2009 Feb 3.

  PMID: 19190116 BACKGROUND

• Huvos AG, Rosen G, Dabska M, Marcove RC. Mesenchymal chondrosarcoma. A clinicopathologic analysis of 35 patients with emphasis on treatment. Cancer. 1983 Apr 1;51(7):1230-7. doi: 10.1002/1097-0142(19830401)51:73.0.co;2-q.

  PMID: 6825046 BACKGROUND

MeSH Terms

Conditions

Chondrosarcoma, Mesenchymal

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Chondrosarcoma; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Silvia Stacchiotti, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvia Stacchiotti, MD

CONTACT

39022390; silvia.stacchiotti@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: September 14, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)