E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Triple Negative Breast Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the objective response rate (ORR) of SAR240550 administered as a 60min intravenous infusion twice weekly (arm A) or weekly (arm B), in combination with gemcitabine/carboplatin chemotherapy regimen in patients with metastatic Triple Negative Breast Cancer (mTNBC) |
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E.2.2 | Secondary objectives of the trial |
To assess the safety profile in arm A and in arm B. To assess the clinical benefit rate (CBR) defined as the rate of complete response (CR), partial response (PR) and stable disease (SD) lasting at least 24 weeks in arm A and in arm B. Progression-free survival (PFS) and the overall survival (OS) in both arms in arm A and in arm B. To evaluate the pharmacokinetic (PK) profile of SAR240550 in both arms (optional). To assess the biological activity of the study treatment on tumor tissue in both arms (optional). To characterize the molecular and biological profile of tumors (optional). To assess the effect of SAR240550 on PAR level on PBMC in both arms (optional). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione:1 Data:2009/10/19 Titolo:Sottostudio molecolare biologico (opzionale) Obiettivi:Saranno effettuati test di farmacogenomica e farmacodinamica in un sottostudio per valutare l`effetto del trattamento in studio sul tumore e sulle concentrazioni PAR (su biopsie tumorali e su cellule mononucleari del sangue periferico)
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2009/10/19 Titolo:studio di farmacocinetica - opzionale Obiettivi:valutazione del profilo farmacocinetico in entrambi i bracci. (opzionale)
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E.3 | Principal inclusion criteria |
Eligible patients must meet the following criteria to be enrolled in the study: I 01.Histologically documented breast cancer (either primary or metastatic site) that is ER- negative, PR-negative (for ER- and PR-negative: <10% tumor staining by immunohistochemistry [IHC]), and HER2 non-overexpressing by immunohistochemistry (0,1) or fluorescence in situ hybridization (FISH negative); I 02.Metastatic breast cancer with measurable disease by RECIST 1.1 criteria; I 03.Prior treatment that includes: - never having received anticancer therapy for metastatic disease OR - having received 1 or 2 prior chemotherapy regimens in the metastatic setting (prior adjuvant/neoadjuvant systemic therapy will be considered as a prior chemotherapy if the first relapse occurred less than 1 year after the last treatment administration); I 04.Female ≥18 years of age; I 05.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; I 06.Organ and marrow function as follows: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/mm3, hemoglobin ≥9g/dL, bilirubin ≤1.0 x ULN, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times x ULN if no liver involvement or ≤5 times x ULN with liver involvement; I 07.Radiation therapy completed at least 7 days before study dosing on day 1; radiated lesions may not serve as measurable disease; I 08.Central nervous system (CNS) metastases allowed if patient does not require steroids, whole brain XRT, gamma/cyber knife, and brain metastases are clinically stable without symptomatic progression; I 09.For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy; I 10.No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a malignancy diagnosed and curatively treated ≥5 years ago); I 11.Capability to understand and comply with the protocol; I 12.Signed informed consent document(s). |
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E.4 | Principal exclusion criteria |
E 01.Systemic anticancer therapy within 14 days of the first dose of study drug; E 02.Prior treatment with gemcitabine, carboplatin, cisplatin or any PARP inhibitor; E 03.Has not recovered to grade ≤1 from AEs per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0; E 04.Bone metastasis or skin metastasis only; E 05.Major medical conditions that might affect study participation (e.g., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease); E 06.Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation is acceptable; E 07.Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention; E 08.Pregnant or breast-feeding women; E 09.Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator or designee. Confirmation of eligibility criteria is required for all potential study patients PRIOR to randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy parameters: The primary efficacy endpoint is the ORR that is defined in the RECIST 1.1 version, as: complete response (CR) rate + partial response (PR) rate. Tumor measurements will be assessed at baseline (within 2 weeks before randomization) and then every 2 cycles (6 weeks) until disease progression. The data will be reviewed by the IRRC |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
due schedule di trattamento - same IMP used at different dosage |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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la fine dello studio sara` approssitivamente 10 mesi dopo la prima dose dell`ultimo paziente incluso. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |