Progressive metastatic breast cancer previously treated in the following subpopulation of patients: Group A: Triple negative phenotype: Estrogen Receptor, Progesterone Receptor and HER-2 negative status (surrogate of basal-like type) Group B: HER-2 overexpressing tumors. Group C: Familial BRCA1 or BRCA2 mutation carriers MedDRA version: 9.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic
Conditions
Interventions
Product Name: YONDELIS® (Trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Current Sponsor code: ET-743
O
Sponsors
Pharma Mar, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient´s written informed consent before any clinical trial-specific procedure. 2. Woman 18 years-of-age or older. 3. Histologically proven diagnosis of progressive metastatic breast cancer either in documented: • Group A: triple negative phenotype [Estrogen Receptor, Progesterone Receptor and HER-2 negative status (surrogate of basal-like type)]. Patients will be eligible if they had received prior therapy with an anthracycline, a taxane and capecitabine, including adjuvant or neoadjuvant therapy, but no more than three prior chemotherapy regimens for metastatic disease. NOTE: re-treatment with the same regimen or its components after a progression-free interval of 6 months or longer will be considered a second regimen. • Group B: HER-2 overexpressing breast cancer. Patients will be eligible if they have progressive metastatic disease following treatment with anthracyclines, taxanes and capecitabine, with trastuzumab or other HER-2 target agent , but no more than three prior chemotherapy regimens for metastatic disease are allowed. NOTE: re-treatment with the same regimen or its components after a progression-free interval of 6 months or longer will be considered as second regimen. • Group C: Familial BRCA1 or BRCA2 mutation carriers. Patients will be eligible if they had received prior therapy with an anthracycline, a taxanes and capecitabine, including adjuvant or neoadjuvant therapy, without prior lines limitation. 4. Measurable disease as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines. If the only indicator lesion is in a previously irradiated area, the recurrence must be biopsy proven. 5. Patients with bone metastases currently receiving biphosphonates for palliation will be eligible if other sites of measurable disease are present. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 7. Hematologic variables: • Hemoglobin =9 g/dL • Absolute neutrophil count (ANC) =1,500/µL, and • Platelet count =100,000/µL. 8. Serum creatinine = 1.5 mg/dL or creatinine clearance = 30 mL/min 9. Creatinine phosphokinase (CPK) = 2.5 ULN. 10. Hepatic function variables • Total bilirubin = ULN. • Total alkaline phosphatase = 2.5 ULN, or if > 2.5 ULN consider alkaline phosphatase liver fraction or GGT or 5’ nucleotidase must be = ULN, if the elevation could be osseous in origin. • AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine transaminase [SGPT]) must be =2.5 x ULN. 11. Albumin = 25 g/l. 12. Adequately recovered from the acute toxicity of any prior treatment 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: Prior exposure to trabectedin. 2. Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone. 3. More than three prior chemotherapy regimens for metastatic disease for group A and B. NOTE:re-treatment with the same regimen or its components after a progression-free interval of 6 months or more is considered a second regimen. 4. Pregnant or lactating women or any women of childbearing potential who is not employing adequate contraception. Acceptable methods of contraception include; IUD, and double barrier (condom with a contraceptive sponge or contraceptive suppository). Use of hormonal contraception is not acceptable during this clinical trial. 5. Less than 4 weeks from radiation therapy or last dose of hormonal therapy, biological therapy, therapy with any investigational agent, or chemotherapy (6 weeks if a nitrosurea or mitomycin C). 6. History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 5 years or longer. 7. Known clinically relevant CNS metastases. 8. Other serious illnesses, such as: • Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrollment; uncontrolled arterial hypertension or arrhythmias • Psychiatric disorder that prevents compliance with protocol • Active viral hepatitis; or chronic liver disease • Active infection • Any other unstable medical conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: to determine the objective response rate by RECIST (Complete and Partial Response [CR + PR]) with trabectedin in patients with the following metastatic breast cancer subtypes: Group A: triple negative profile (ER-,PR-,HER-2-) Group B: human epidermal growth factor receptor-2 overexpressing tumors (HER-2+) Group C: familial BRCA1 or BRCA2 mutation carriers;Secondary Objective: To assess in each group: • Duration of response • Progression-free survival • Exploratory evaluation of changes in tumor volume (three dimensional analysis) and changes in tumoral radiological density • Safety profile in this patient population • Exploratory, hypothesis-generating pharmacogenomic analyses to correlate molecular parameters in patient samples with clinical outcomes (objective response and PFS) within and across patient strata.;Primary end point(s): Confirmed objective tumor response (CR or PR) rate (RECIST) in each group. Each patient will be assigned one of the following categories: Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) Reasons for non-evaluability will be subdivided into the following categories: 1) ‘early toxicity’ (as reason for withdrawal without on-/end-oftreatment tumor assessment available) 2) ‘never treated’ (no on-/end-of-treatment tumor assessment available) 3) ‘other’ (e.g., no baseline tumor assessment, technical reasons, absence of on-/end-of-treatment tumor assessment for other reasons than ‘death’, ‘early toxicity’ or ‘never treated’, consent withdrawal before evaluation,) To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeated assessments that should be performed no less than 4 weeks after the criteria for response are first met. | — |
Countries
France, Italy, Poland
Outcome results
None listed