Translocation-Related Sarcomas MedDRA version: 9.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas
Conditions
Interventions
Trade Name: Yondelis® 0.25 mg and Yondelis® 1 mg
Product Name: Yondelis
Product Code: ET-743
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trabectedin
CAS
Sponsors
Pharma Mar, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patient’s written informed consent before any study-specific procedures. 2) Adult patients (age = 18 years). 3) Pathological diagnosis of TRS (institutional assessment), including the following subtypes: alveolar rhabdomyosarcoma, alveolar soft part sarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, endometrial stromal sarcoma (prior hormone therapy allowed), low grade fibromyxoid sarcoma, myxoid chondrosarcoma, MRCL and synovial sarcoma. Availability of adequate tumor material for external review is mandatory. 4) Patients must have unresectable, locally advanced or metastatic disease prior to enrolment. 5) ECOG PS score of 0-2. 6) Adequate cardiac function, defined as LVEF within normal limits according to institutional standards, as shown by echocardiography or scintigraphy (MUGA). 7) Hematological variables: a) Hemoglobin = 9 g/dl. b) ANC = 1,500/µl. c) Platelet count = 100,000/µl. 8) Biochemical variables: a) Serum creatinine = 1.5 mg/dl b) CPK = 2.5 x ULN. 9) Hepatic function variables: a) Total bilirubin = ULN. b) Total AP = 2.5 x ULN, or if > 2.5 x ULN consider AP liver fraction, and/or GGT, and/or 5’ nucleotidase must be = ULN, c) AST/SGOT and ALT/SGPT must be = 2.5 x ULN, d) Albumin = 25 g/l. Are the trial subjects under 18? no 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Known hypersensitivity to any of the components of the i.v. formulation of trabectedin or the comparators. 2) Prior chemotherapy treatment. 3) Prior irradiation of the lesion if only one target lesion (i.e., measurable) is available. 4) Pregnant or lactating women or men and women of reproductive potential who are not using effective contraceptive methods (one or more of the following): a) Complete abstinence from intercourse from two weeks prior to administration of the study treatment, throughout the study, and for at least six months after completion or premature discontinuation from the study to account for elimination of the investigational drug(s); or, b) Physical sterilization of the patient or the patient’s partner; or, c) One of the following, for female patients or female partners of male patients: - Implants of levonorgestrel; or, - Injectable progestogen; or, - Oral contraceptive (combined or progestogen only; patients taking oral contraceptives should have been on a stable regimen for at least two months prior to screening), or, - Any IUD with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, - Double barrier method (two physical barriers or one physical barrier plus spermicide); or, - Any other methods with published data showing that the lowest expected failure rate for that method is less than 1% per year. 5) History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for five years or more. 6) Brain metastases and/or leptomeningeal metastases, even if treated. 7) Other serious illnesses, such as: a) Congestive heart failure or angina pectoris; myocardial infarction within one year before enrolment; uncontrolled arterial hypertension (according to WHO criteria), arrhythmias or abnormal LVEF. 8) Psychiatric disorder or any other personal circumstances that prevent compliance with the study protocol. 9) Active viral hepatitis or chronic liver disease. 10) Active infection. 11) Any other unstable medical condition. 12) Inability or unwillingness to comply with the study protocol. 13) Prior treatment with any investigational drugs/treatments within 30 days before inclusion into the current study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary end point: o PFS: will be calculated as the time from the date of randomization to the date of documented PD or death (regardless of the cause of death). If the patient receives further antitumor therapy before PD and within the timeframe expected for first follow-up, PFS will be censored on the date of administration of this antitumor therapy. If the patient is lost to follow-up for the assessment of progression, or has more than one missing follow-up between the date of last tumor assessment and the date of death or further antitumor therapy, the PFS will be censored at the date of last tumor assessment. Secondary end points: • Best objective response: will be the best response obtained in any evaluation according to RECIST, done at least six weeks after randomization. • PFS at six months: will be the Kaplan-Meier estimate of the probability of being free from progression and death at six months. • OS: will be calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival will be censored on that date). • Duration of response: will be calculated from the date of first documentation of response (CR or PR, whichever comes first) to the date of documented PD or death. The censoring rules defined above for PFS will be used for duration of response. • Exploratory CT evaluations: performed by Choi response criteria (52) and correlation with RECIST response. • Saftey profile: The AEs, SAEs, laboratory evaluations, deaths and study discontinuations due to AEs will be analyzed as described in Section 9.3. • Exploratory, pharmacogenomic studies: fusion protein type and variants, and DNA-repair markers will be correlated with clinical outcomes.;Main Objective: To evaluate the efficacy of trabectedin vs. standard DXCT as first-line treatment of patients with advanced TRS, by comparing PFS in each treatment arm.;Secondary Objective: •To compare 6-month PFS rates. • To compare response rates an | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed