Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-),HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers. - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-000794-31-IT
• Date of registration: 09/10/2007
• Prospective Registration: Yes
• Primary sponsor: PHARMA MAR
• Public title: Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-),HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers. - ND
• Scientific title: Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-),HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers. - ND
• Date of first enrolment: 13/11/2007
• Target sample size: 321
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000794-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Open-label, prospettico If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Italy, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
1.PatientŽs 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 more than or equal to 9 g/dL Absolute neutrophil count (ANC) more than or equal to 1,500/µL, and Platelet count more than or equal to 100,000/µL. 8. Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance more than or equal to 30 mL/min 9. Creatinine phosphokinase (CPK) less than or equal to 2.5 ULN. 10. Hepatic function variables Total bilirubin less than or equal to ULN. Total alkaline phosphatase less than or equal to 2.5 ULN, or if > 2.5 ULN consider alkaline phosphatase liver fraction or GGT or 5? nucleotidase must be less than or equal to ULN, if the elevation could be osseous in origin. AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine transaminase [SGPT]) must be less than or equal to 2.5 x ULN. 11 Albumin more than or equal to 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:
1.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 ble during this clinical trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Metastatic Breast Cancer with triple negative profile (ER-, PR-, HER2-),HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers.
MedDRA version: 6.1 Level: PT Classification code 10055113

Intervention(s)

Product Name: YONDELIS (trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Current Sponsor code: ET-743 (Ecteinascidin 743)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: .25-

Product Name: YONDELIS (trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Current Sponsor code: ET-743 (Ecteinascidin 743)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

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

Primary end point(s): L'efficacia verra' valutata stabilendo la risposta obiettiva e PFS. La malattia misurabile e i criteri di risposta utilizzati in questo protocollo sono stati definiti dalle linee guide RECIST.

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.

Secondary ID(s)

2007-000794-31-FR

ET-B-027-06