Study of SAR240550 (BSI-201) in Combination With Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Breast Cancer

Breast Cancer, Metastatic Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045304
• Other study ID #: TCD11418
• Secondary ID: 2009-016091-80
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2010
• Last updated: January 13, 2014
• Start date: February 2010
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• To assess the objective response rate (ORR) of iniparib (SAR240550) administered as a 60min intravenous (IV) infusion twice weekly or weekly, in combination with gemcitabine/carboplatin chemotherapy regimen in patients with metastatic Triple Negative Breast Cancer (mTNBC).

Secondary Objectives:

• 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;

• To assess Progression-free survival (PFS) and the overall survival (OS);

• To assess the safety profile of each schedule of iniparib;

• To assess the biological activity in tumor tissue (substudy);

• To evaluate the pharmacokinetic (PK) profile of iniparib (substudy);

• To characterize molecular and biological profile of tumors (substudy);

• To assess the effect of iniparib on poly(ADP)-ribose (PAR) level in peripheral blood mononuclear cells (PBMC) (substudy).

Description:

The duration of the study for a patient includes a period for inclusion of up to 3 weeks. The patients may continue treatment until disease progression, unacceptable toxicity or consent withdrawal, followed by a minimum of 30-day follow-up after the last study treatment administration.

In case of discontinuation of study treatment, the patient will be considered as withdrawn from study treatment, and will be followed as planned for at least 30 days after the last administration of study treatment for safety purpose. In case of study treatment discontinuation without disease progression, efficacy data will be collected every 6 weeks until disease progression, death or end of study whatever comes first. After disease progression, the patient will be followed-up every 12 weeks (3 months) for overall survival until death or end of study.

The patients who benefit from the study treatment can continue until disease progression, toxicity or willingness to stop.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: November 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Histologically documented breast cancer (either primary or metastatic site) that is ER (estrogen receptor)-negative, PgR (progesterone receptor)-negative ( <10% tumor staining by immunohistochemistry [IHC]) and HER2 (human epidermal growth factor 2) non-overexpressing by IHC (0,1+) or, IHC 2+ and FISH (fluorescence In situ hybridization) negative.

• Metastatic breast cancer with measurable disease by the revised guideline for Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1 criteria);

• 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 is considered as a prior chemotherapy if the first relapse occurred less than one year after the last treatment administration).

Exclusion criteria:

• Prior treatment with gemcitabine, carboplatin, cisplatin or any PARP inhibitor;

• Bone metastasis as only disease location (except for bone metastasis with measurable soft tissue component);

• Major medical conditions that might affect study participation e.g., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer, Metastatic
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Iniparib
Pharmaceutical form: solution for infusion Route of administration: intravenous
• Gemcitabine
Pharmaceutical form: solution for infusion Route of administration: intravenous
• Carboplatin
Pharmaceutical form: solution for infusion Route of administration: intravenous

Locations

Country	Name	City	State
Australia	Sanofi-Aventis Investigational Site Number 036002	Parkville
Australia	Sanofi-Aventis Investigational Site Number 036001	Perth
Australia	Sanofi-Aventis Investigational Site Number 036003	Westmead
Belgium	Sanofi-Aventis Investigational Site Number 056001	Bruxelles
Belgium	Sanofi-Aventis Investigational Site Number 056002	Leuven
France	Sanofi-Aventis Investigational Site Number 250005	Besancon Cedex
France	Sanofi-Aventis Investigational Site Number 250003	Bordeaux
France	Sanofi-Aventis Investigational Site Number 250002	Dijon
France	Sanofi-Aventis Investigational Site Number 250004	Paris
France	Sanofi-Aventis Investigational Site Number 250006	Paris Cedex 05
France	Sanofi-Aventis Investigational Site Number 250001	Toulouse
Italy	Sanofi-Aventis Investigational Site Number 380004	Genova
Italy	Sanofi-Aventis Investigational Site Number 380001	Milano
Italy	Sanofi-Aventis Investigational Site Number 380002	Modena
Italy	Sanofi-Aventis Investigational Site Number 380003	Udine
Netherlands	Sanofi-Aventis Investigational Site Number 528001	Rotterdam
Spain	Sanofi-Aventis Investigational Site Number 724002	Barcelona
Spain	Sanofi-Aventis Investigational Site Number 724004	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724001	Málaga
Spain	Sanofi-Aventis Investigational Site Number 724003	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Australia,  Belgium,  France,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	Proportion of participants with confirmed complete response (CR) or partial response (PR) as confirmed by an Independent Radiology Review Committee (IRRC) based on central review of scans in a blinded manner.	Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months)	No
Secondary	Clinical benefit rate (CBR)	Proportion of participants with confirmed complete response (CR) or partial response (PR) ot stable disease (SD) greater than 24 weeks as confirmed by the IRRC.	Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months)	No
Secondary	Progression-free survival	Number of days from the date of randomization to the date of disease progression (ie, radiological progression based on IRRC assessment) or the date of death (from any cause), whichever is earlier.	Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months)	No
Secondary	Overall survival		Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months)	No