Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

Mesenchymal Chondrosarcoma Clinical Trial

— ISG-MCS  

Official title:

Phase II Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04305548
• Other study ID #: ISG-MCS
• Status: Recruiting
• Phase: Phase 2
• Start date: September 14, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: Italian Sarcoma Group
• Contact: Silvia Stacchiotti, MD
• Phone: 39022390
• Email: silvia.stacchiotti[@]istitutotumori.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: December 31, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chondrosarcoma
• Mesenchymal Chondrosarcoma

Intervention

Drug:
• 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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Italian Sarcoma Group	PharmaMar

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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