Study on advanced rearranged Mesenchymal chondrosarcoma
- Conditions
- Patients with advanced, histological and molecularly (presence of the HEY1-NCOA2 fusion) centrally confirmed diagnosis of MCS, with an evidence of RECIST progression within the 6 months prior to starting the study treatment and pre-treated with anthracycline-based chemotherapyMedDRA version: 20.0Level: HLTClassification code 10041298Term: Soft tissue sarcomas histology unspecifiedSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003733-41-IT
- Lead Sponsor
- ITALIAN SARCOMA GROUP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
1.Age = 16 years old
2.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)
3.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
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. 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
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
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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 (= NCI CTCAE v5.0 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 (i.e. congestive heart failure, myocardial infarction within 6 months of study)
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 of 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 (NCI-CTCAE v 5.0) 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to explore the activity of trabectedin from 2nd to 4th line, in patients aged ¿ 16 years with advanced HEY1-NOCA2 positive MCS pre-treated with anthracycline-based chemotherapy. Therefore, with reference to a study population of patients with progressive by RECIST v1.1, locally advanced or metastatic, HEY1-NCOA2 positive MCS pre- treated with one, two or three lines of medical treatment, the primary end-point of the study will be to assess:;Secondary Objective: 1.Choi Response Rate<br>2.Overall Survival (OS)<br>3.Progression Free Survival (PFS)<br>4.Clinical Benefit Rate<br>5.Duration of response<br>6.Safety<br><br>;Primary end point(s): Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;Timepoint(s) of evaluation of this end point: Every 6 weeks up to week 18, then every 12 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall Survival; Progression Free Survival; Duration of response; Adverse events related to the treatment; Choi criteria response rate;Timepoint(s) of evaluation of this end point: Overall Survival: At 3 and 5 years; Progression Free Survival (PFS) At 3 and 5 years; Duration of response At weeks 6, 12,18, 30, 42; Adverse events related to the treatment : at each cycle; Choi criteria response rate At weeks 6, 12,18, 30, 42