TRABECTEDIN for Mesenchymal chondrosarcoma | HEY1-NCOA2-positive mesenchymal chondrosarcoma | Advanced/metastatic mesenchymal chondrosarcoma

Inclusion criteria

• {"criterion_text":"- Age ≥ 16 years old\n- Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and thereafter, at the end of study treatment, for 3 months in female patients of childbearing potential and for 5 months in men in fertile age\n- Cardiac ejection fraction ≥50% as measured by echocardiogram\n- No history of arterial and/or venous thromboembolic event within the previous 12 months\n- The patient or legal representative must be able to read and understand the informed consent form (ICF) 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.\n- Histological centrally confirmed diagnosis of skeletal or extra-skeletal MCS with the documented presence of HEY1-NCOA2 fusion (a paraffin embedded tumour block is required for centralized review)\n- Locally advanced disease (i.e. surgical resection of local disease unfeasible radically or unaccepted by the patient or amenable to become less demolitive or feasible or easier after cytoreduction) and/or metastatic disease\n- Measurable or evaluable disease with RECIST v1.1\n- Evidence of progression by RECIST v1.1 during the 6 months before study entry\n- 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\n- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2\n- Adequate bone marrow function (Blood transfusions to reach the baseline requested Hb level are not allowed)\n- Adequate organ function"}

Exclusion criteria

• {"criterion_text":"- 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\n- Known brain metastasis\n- Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis)\n- Known diagnosis of human deficiency virus (HIV) infection\n- Active or chronic hepatitis B or C requiring treatment with antiviral therapy\n- Medical history of hemorrhage or a bleeding event ≥ Grade 3 (NCI‐CTCAE v 5.0) within 4 weeks prior to the initiation of study treatment\n- 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\n- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs\n- Any other factors, that, at judgment of investigator, could affect the safety of the patients according to the available trabectedin safety data\n- Expected non-compliance to medical regimens\n- 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\n- Previous radiotherapy to 25% of the bone marrow\n- Major surgery within 2 weeks prior to study entry\n- 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.\n- Persistent toxicities (≥ NCI CTCAE v5.0 grade 2) with the exception of alopecia, caused by previous anticancer therapies.\n- Pregnancy or breast feeding\n- Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e. congestive heart failure, myocardial infarction within 6 months of study)\n- 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"}

Primary endpoints

• {"endpoint_text":"- Overall tumour Response Rate, according to RECIST v 1.1","definition_or_measurement_approach":"Overall tumour response assessed according to RECIST v1.1 (as stated: primary end-point will be to assess Overall tumour Response Rate, according to RECIST v 1.1 in patients with progressive disease by RECIST v1.1)."}

Secondary endpoints

• {"endpoint_text":"- Choi Response Rate","definition_or_measurement_approach":"Response assessed according to Choi criteria."}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Standard overall survival measurement (time from study entry to death)."}
• {"endpoint_text":"- Progression Free Survival (PFS)","definition_or_measurement_approach":"Progression-free survival per disease progression criteria (RECIST v1.1)."}
• {"endpoint_text":"- Clinical Benefit Rate","definition_or_measurement_approach":"Defined in objectives as RECIST CR + PR + SD > 6 months (clinical benefit rate)."}
• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":"Duration of response as standard (time from response to progression or death)."}
• {"endpoint_text":"- Safety","definition_or_measurement_approach":"Toxicity profile evaluated (NCI-CTCAE v5.0 referenced elsewhere for grading adverse events)."}
• {"endpoint_text":"- Exploration of transcriptomic and genomic profile of responsive versus unresponsive tumors. Genomic, mRNA, miRNA expression pattern of a sizable number of responsive and unresponsive tumors will be analyzed and compared.","definition_or_measurement_approach":"Transcriptomic and genomic analyses comparing expression profiles (genomic, mRNA, miRNA) of responsive vs unresponsive tumors."}
• {"endpoint_text":"- Evaluation of efficacy of liquid biopsy (measure of HEY1-NCOA2 fusion in cell free DNA/RNA) in anticipating response/progression under treatment.","definition_or_measurement_approach":"Measurement of HEY1-NCOA2 fusion in cell-free DNA/RNA (liquid biopsy) to evaluate ability to anticipate response or progression."}
• {"endpoint_text":"- Validazione dei target trascrizionali HEY1-NCOA2 coinvolti nella risposta MCS alla trabectedina mediante esperimenti in vitro.","definition_or_measurement_approach":"Validation of HEY1-NCOA2 transcriptional targets involved in MCS response to trabectedin via in vitro experiments."}

Italy

Earliest CTIS Part Ii Submission Date

31-05-2024

Latest Decision Or Authorization Date

02-07-2024

Processing Time Days

32

Number Of Sites

7

Number Of Participants

20

Primary sponsor

Full Name

Italian Sarcoma Group

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Pharma Mar S.A.","duties_or_roles":"Monetary support","organisation_type":""}