Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

NCT ID: NCT04305548

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-14

Study Completion Date

2025-12-01

Brief Summary

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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

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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.

Conditions

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Mesenchymal Chondrosarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Trabectedin

Intervention Type 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

Interventions

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Trabectedin

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PharmaMar

INDUSTRY

Sponsor Role collaborator

Italian Sarcoma Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Silvia Stacchiotti, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Locations

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Nuovo Ospedale di Prato

Prato, Firenze, Italy

Site Status RECRUITING

Policlinico Universitario Campus Biomedico

Roma, RM, Italy

Site Status NOT_YET_RECRUITING

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Site Status RECRUITING

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, , Italy

Site Status RECRUITING

Fondazione IRCSS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

Ospedale Giaccone

Palermo, , Italy

Site Status RECRUITING

Istituti Fisioterapici Ospitalieri - Ospedale Regina Elena

Roma, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Silvia Stacchiotti, MD

Role: CONTACT

Phone: 39022390

Email: [email protected]

Facility Contacts

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Giacomo G. Baldi, MD

Role: primary

Bruno Vincenzi, MD

Role: primary

Sandra Aliberti, MD

Role: primary

Toni Ibrahim, MD

Role: primary

Silvia Stacchiotti, MD

Role: primary

Giuseppe Badalamenti, MD

Role: primary

Virginia Ferraresi, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 21084965 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22034177 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27418251 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19190116 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6825046 (View on PubMed)

Other Identifiers

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ISG-MCS

Identifier Type: -

Identifier Source: org_study_id