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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01045304
First received: January 7, 2010
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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).

Condition Intervention Phase
Breast Cancer, Metastatic
Drug: Iniparib
Drug: Gemcitabine
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Clinical benefit rate (CBR) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Progression-free survival [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Overall survival [ Time Frame: 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) ] [ Designated as safety issue: No ]

Enrollment: 163
Study Start Date: February 2010
Study Completion Date: November 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gencitabine + iniparib twice weekly

Gemcitabine, 1000 mg/m² IV over 30 minutes and carboplatin, area under the curve (AUC) = 2, IV over 60 minutes, both on Days 1 and 8 of 3-week cycles.

Iniparib, 5.6 mg/kg IV over 60 minutes on Days 1, 4, 8 and 11 of 3-week cycles

Drug: Iniparib

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Names:
  • SAR240550
  • BSI-201
Drug: Gemcitabine

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Drug: Carboplatin

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Experimental: Gencitabine + iniparib weekly

Gemcitabine, 1000 mg/m² IV over 30 minutes and carboplatin, area under the curve (AUC) = 2, IV over 60 minutes, both on Days 1 and 8 of 3-week cycles.

Iniparib, 11.2 mg/kg IV over 60 minutes on Days 1 and 8 of 3-week cycles

Drug: Iniparib

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Names:
  • SAR240550
  • BSI-201
Drug: Gemcitabine

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Drug: Carboplatin

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01045304

Locations
Australia
Sanofi-Aventis Investigational Site Number 036002
Parkville, Australia, 3052
Sanofi-Aventis Investigational Site Number 036001
Perth, Australia, 6000
Sanofi-Aventis Investigational Site Number 036003
Westmead, Australia, 2145
Belgium
Sanofi-Aventis Investigational Site Number 056001
Bruxelles, Belgium, 1000
Sanofi-Aventis Investigational Site Number 056002
Leuven, Belgium, 3000
France
Sanofi-Aventis Investigational Site Number 250005
Besancon Cedex, France, 25030
Sanofi-Aventis Investigational Site Number 250003
Bordeaux, France, 33076
Sanofi-Aventis Investigational Site Number 250002
Dijon, France, 21034
Sanofi-Aventis Investigational Site Number 250004
Paris, France, 75970
Sanofi-Aventis Investigational Site Number 250006
Paris Cedex 05, France, 75231
Sanofi-Aventis Investigational Site Number 250001
Toulouse, France, 31052
Italy
Sanofi-Aventis Investigational Site Number 380004
Genova, Italy, 16132
Sanofi-Aventis Investigational Site Number 380001
Milano, Italy, 20133
Sanofi-Aventis Investigational Site Number 380002
Modena, Italy, 41100
Sanofi-Aventis Investigational Site Number 380003
Udine, Italy, 33100
Netherlands
Sanofi-Aventis Investigational Site Number 528001
Rotterdam, Netherlands, 3075 EA
Spain
Sanofi-Aventis Investigational Site Number 724002
Barcelona, Spain, 08035
Sanofi-Aventis Investigational Site Number 724004
Madrid, Spain, 28050
Sanofi-Aventis Investigational Site Number 724001
Málaga, Spain, 29010
Sanofi-Aventis Investigational Site Number 724003
Valencia, Spain, 46010
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01045304     History of Changes
Other Study ID Numbers: TCD11418, 2009-016091-80
Study First Received: January 7, 2010
Last Updated: January 13, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Carboplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014