Advanced Breast Carcinoma MedDRA version: 14.0 Level: LLT Classification code 10006204 Term: Breast carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Yondelis 0.25 mg powder for concentrate for solution for infusion.
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: trabectedine
Concentration uni
Sponsors
Pharma Mar, S.A. Sociedad Unipersonal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Voluntary written informed consent, obtained from the patient before the beginning of any specific study procedures. 3. Histologically proven diagnosis of advanced or MBC. 4. Patients must be HER2 negative and hormone receptors (estrogen receptor and/or progesterone receptor) positive. 5. Failure to at least two but no more than five chemotherapy lines in the advanced setting. 6. Previous treatment with anthracyclines or taxanes. 7. XPG RNA expression determined from patient's tumor specimen (paraffinembedded tissue). 8. Measurable disease as defined by the RECIST v.1.1. If the only tumor lesion is situated in a previously irradiated area, or in an area subjected to other locoregional therapy, progression in the lesion must be demonstrated. 9. Patients with bone metastases currently receiving bisphosphonates for palliation will be eligible if other sites of measurable disease are present. 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see Appendix 1). 11. Adequate bone marrow, liver and kidney function: a. Hemoglobin = 9g/dl. b. Neutrophil count = 1.5×109/l. c. Platelet count = 100×109/l d. Serum creatinine = 1.5 mg/dl or calculated creatinine clearance = 30 ml/min. e. Albumin =2.5g/dl. f. Total serum bilirubin = upper limit of normal (ULN), except in case of Gilbert's syndrome. g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3×ULN. h. Total alkaline phosphatase (AP) =2.5×ULN; if the value is >2.5×ULN, evaluate the hepatic AP isoenzyme and/or gamma-glutamyltransferase (GGT) and/or 5'nucleotidase, which values must be within the ULN (this indicates that the elevation of AP was of bone origin). i. Creatine phosphokinase (CPK) =2.5×ULN. 12. Life expectancy =3 months. 13. Complete recovery to grade = 1 from any toxicity due to previous therapy (except for alopecia and grade 2 neuropathy). 14. Women of child-bearing potential must have a negative pregnancy test prior to the treatment initiation and use a medically approved method of contraception during treatment with the trial medication and for three months after the last administration of the study drug. Fertile men must use a medically approved method of contraception during the treatment with the trial medication and for five months after the last administration of the study drug. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Patients fulfilling any of the following criteria will not be included into the trial: 1. Prior exposure to trabectedin. 2.Treatment with chemotherapy or with biological agents in the two weeks prior to the first dose of the clinical trial drug (six weeks for nitrosoureas or mitomycin C) provided that patients have recovered to grade = 1 from any toxicity due to prior therapy (except alopecia and grade 2 neuropathy)(see inclusion criterion 13). 3. Participation in another clinical trial, or concomitant treatment with any investigational drug, in the four weeks prior to enrollment in the clinical trial. 4. Concomitant administration of any other antineoplastic therapy. 5. Contraindications to corticosteroid use. 6. History of another neoplastic disease (except for basal cell carcinoma of the skin or properly treated carcinoma in situ of the uterine cervix) unless in remission for five years or longer. 7. Presence of cerebral and/or leptomeningeal metastasis, even if they are being treated. 8. Other serious and/or relevant diseases or clinical situations that, in opinion of the Investigator, are incompatible with the protocol (any of the following): a. History of cardiac disease, such as myocardial infarction, in the year prior to enrollment in the clinical trial; symptomatic/uncontrolled angina pectoris; congestive heart failure or uncontrolled cardiac ischemia; any type of uncontrolled arrhythmia or abnormal left ventricular ejection fraction, or uncontrolled arterial hypertension (according to the standards of the World Health Organization [WHO]). b. History of significant psychiatric disease. c. Active infection requiring antibiotic, antifungal or antiviral treatment that, in the opinion of the Investigator, could compromise the patient's capacity to tolerate the therapy. d. Active liver (hepatitis B or C) or renal disease. e. Major surgery in the two weeks prior to entering the clinical trial, or any other concomitant pathology that could jeopardize the patient's safety or commitment to complete the clinical trial. 9. Pregnant or breastfeeding women (negative pregnancy test in the three days prior to treatment administration required). 10. Inability or refusal to comply with the protocol or with the clinical trial procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy in terms of progression-free survival rate at 4 months (PFS4) of trabectedin in patients with advanced or MBC, hormonal receptors positive, HER2 negative, positive or negative for XPG overexpression, who have already received at least two lines of chemotherapy for advanced disease (including anthracyclines and taxanes).;Secondary Objective: To compare progression-free survival (PFS), objective response rate (ORR) and duration of response (DR), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST, v.1.1) in patients positive or negative for XPG overexpression. To compare overall survival in patients positive or negative for XPG overexpression. Safety profile.;Primary end point(s): The primary endpoint of this study is the progression-free survival rate at 16 weeks (PFS4), defined as the percentage of patients remaining alive and progression-free at Week 16 after the first treatment dose.;Timepoint(s) of evaluation of this end point: Main analysis of PFS4 will be done when 50 evaluable patients are recruited in each XPG stratum. Futility analyses are planned once 20 evaluable patients are enrolled in each XPG stratum. Each analysis will be performed using the O'Brien Fleming boundary, after evaluable patients have had a tumor assessment at Week 16 or PD or died due to disease progression or discontinued treatment due to unmanageable toxicity, whichever occurs first. The minimum follow-up to do this analysis will be 16 weeks after the last patient recruited has received the first trabectedin infusion. The patient’s survival will be assessed every three months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare progression-free survival (PFS), overall response rate (ORR) and duration of response (DR), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST, v.1.1) in patients positive or negative for XPG overexpression. To compare overall survival in patients positive or negative for XPG overexpression. Safety profile.;Timepoint(s) of evaluation of this end point: Secondary endpoints (if applicable) would be assessed at the same time than primary endpoint analysis. The planned study termination (clinical cut-off) is: Four months after the first infusion of the last evaluable patient recruited if the trial is stopped at the first stage. Three months after the last infusion administered if the study proceeds into the second stage. The patient’s survival will be assessed every three months. | — |
Countries
Belgium, Spain
Contacts
Public ContactClinical Trials
PharmaMar S.A. Sociedad Unipersonal
Outcome results
None listed