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

• ClinicalTrials.gov Identifier: NCT01045304
• Recruitment Status: Completed
• First Posted: January 11, 2010
• Last Update Posted: January 14, 2014
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: January 7, 2010
• First Posted Date: January 11, 2010
• Last Update Posted Date: January 14, 2014
• Study Start Date: February 2010
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2014)

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) ]

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.

• Original Primary Outcome Measures (submitted: January 8, 2010): Overall response rate (ORR) as defined in the RECIST 1.1 version, as: complete response (CR) rate and partial response (PR) rate [ Time Frame: up to a maximum follow up of 14 months ]

Current Secondary Outcome Measures (submitted: January 13, 2014)

• 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) ]
  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) ]
  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) ]

Original Secondary Outcome Measures (submitted: January 8, 2010)

• Clinical benefit rate (CBR) defined in the RECIST 1.1 version, as complete response (CR) rate + partial response (PR) rate+ stable disease (SD)≥24weeks rate [ Time Frame: up to a maximum follow up of 14 months ]
• Progression - free survival assessed according to RECIST 1.1 version [ Time Frame: up to a maximum follow up of 20 months ]
• Overall survival [ Time Frame: up to a maximum follow up of 20 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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).

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer, Metastatic

Intervention

• 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

Study Arms

• 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

  Interventions:

  • Drug: Iniparib
  • Drug: Gemcitabine
  • Drug: Carboplatin
• 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

  Interventions:

  • Drug: Iniparib
  • Drug: Gemcitabine
  • Drug: Carboplatin

• Publications *: Dieras V, Bonnefoi H, Alba E, Awada A, Coudert B, Pivot X, Gligorov J, Jager A, Zambelli S, Lindeman GJ, Charpentier E, Emmons GT, Garcia-Ribas I, Paridaens R, Verweij J. Iniparib administered weekly or twice-weekly in combination with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer: a phase II randomized open-label study with pharmacokinetics. Breast Cancer Res Treat. 2019 Sep;177(2):383-393. doi: 10.1007/s10549-019-05305-w. Epub 2019 Jun 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2012): 163
• Original Estimated Enrollment (submitted: January 8, 2010): 80
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Italy, Netherlands, Spain

Administrative Information

• NCT Number: NCT01045304
• Other Study ID Numbers: TCD11418; 2009-016091-80 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanofi
• Original Responsible Party: International Clinical Development Study Director, sanofi-aventis
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: January 2014