Mesenchymal Chondrosarcoma
Conditions
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.
Interventions
DRUGTrabectedin
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
Sponsors
Italian Sarcoma Group
PharmaMar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Choi criteria response rate | At weeks 6, 12,18, 30, 42 | Response rate according Choi criteria |
| Overall Survival | At 3 and 5 years | Proportion of patients who are still alive at 36 and 60 months after have started the treatment |
| Progression Free Survival (PFS) | At 3 and 5 years | Survival without disease progression |
| Clinical Benefit Rate | Month 6 | Proportion of patient alive, without disease progression, after 6 months of 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 |
| 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 |
Countries
Italy
Contacts
CONTACTSilvia Stacchiotti, MD
PRINCIPAL_INVESTIGATORSilvia Stacchiotti, MD
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Outcome results
None listed