Multicenter, randomized, open label study evaluating a poly(ADP-ribose) polymerase-1(PARP-1) inhibitor, SAR240550 (BSI-201), administered twice weekly or weekly, in combination with gemcitabine/carboplatin, in patients with metastatic Triple Negative Breast Cancer (mTNBC)

• Register: EUCTR
• Last refreshed on: 18 August 2014
• Main ID: EUCTR2009-016091-80-BE
• Date of registration: 23/11/2009
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: Multicenter, randomized, open label study evaluating a poly(ADP-ribose) polymerase-1(PARP-1) inhibitor, SAR240550 (BSI-201), administered twice weekly or weekly, in combination with gemcitabine/carboplatin, in patients with metastatic Triple Negative Breast Cancer (mTNBC)
• Scientific title: Multicenter, randomized, open label study evaluating a poly(ADP-ribose) polymerase-1(PARP-1) inhibitor, SAR240550 (BSI-201), administered twice weekly or weekly, in combination with gemcitabine/carboplatin, in patients with metastatic Triple Negative Breast Cancer (mTNBC)
• Date of first enrolment: 10/03/2010
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016091-80
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, France, Italy, Netherlands, Spain

Key inclusion & exclusion criteria

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 IHC (0,1+) or IHC 2+ and fluorescence in situ hybridization (FISH negative). Patients IHC 3+ are not eligible;
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 neo-adjuvant/adjuvant systemic therapy will be considered as a prior chemotherapy if the first relapse occurred less than 1 year after the last treatment administration). Platinum compounds are allowed as prior neo-adjuvant/adjuvant therapy if the first relapse occured more than 1 year after the last 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, total bilirubin =1.0 x ULN (total bilirubin =1.5 x ULN is allowed in case of Gilbert's syndrome provided AST and ALT <1.5 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 and during 3 months after the last study treatment administration;
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).
I 13. Patient with skin lesions are eligible provided at least one of the lesions is 10mm calliper measurement at baseline with photography available or measurable on CT scan;
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:
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 (except for alopecia);
E 04. Bone metastasis as only disease location (except for bone metastasis with measurable soft tissue component);
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 (7 days wash-out period is requested before receiving the study treatment);
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.
E 10. Patients with history of lesions of mixed ER/PR/HER2 phenotypes or history of non TNBC


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

Health Condition(s) or Problem(s) studied

Metastatic Triple Negative Breast Cancer.
MedDRA version: 12.0 Level: PT Classification code 10055113 Term: Breast cancer metastatic

Intervention(s)

Product Code: SAR240550 (BSI-201)
Pharmaceutical Form: Solution for infusion
Current Sponsor code: SAR240550 (BSI-201)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Gemcitabine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Gemcitabine
CAS Number: 95058-81-4
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Carboplatin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Gemcitabine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: 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).

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 3 weeks before the first study treatment administration) and then every 2 cycles (6 weeks) until disease progression or death or end of study whichever comes first. The data will be reviewed by the IRRC.

Secondary Objective: •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).

Secondary ID(s)

2009-016091-80-FR

TCD11418