Clinical trial NCT01045304: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer, Metastatic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-01-11
Enrollment: 163
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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In case of discontinuation of study treatment, the patient will be considered as withdrawn from study treatment, and will be followed as planned for at least 30 days after the last administration of study treatment for safety purpose.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.

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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 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)
Secondary outcomes:
measure: Clinical benefit rate (CBR)
timeFrame: 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)
measure: Progression-free survival
timeFrame: 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)
measure: Overall survival
timeFrame: 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)
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036002
city: Perth
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036001
city: Westmead
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036003
city: Bruxelles
country: Belgium
facility: Sanofi-Aventis Investigational Site Number 056001
city: Leuven
country: Belgium
facility: Sanofi-Aventis Investigational Site Number 056002
city: Besancon Cedex
country: France
facility: Sanofi-Aventis Investigational Site Number 250005
city: Bordeaux
country: France
facility: Sanofi-Aventis Investigational Site Number 250003
city: Dijon
country: France
facility: Sanofi-Aventis Investigational Site Number 250002
city: Paris Cedex 05
country: France
facility: Sanofi-Aventis Investigational Site Number 250006
city: Paris
country: France
facility: Sanofi-Aventis Investigational Site Number 250004
city: Toulouse
country: France
facility: Sanofi-Aventis Investigational Site Number 250001
city: Genova
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380004
city: Milano
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380001
city: Modena
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380002
city: Udine
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380003
city: Rotterdam
country: Netherlands
facility: Sanofi-Aventis Investigational Site Number 528001
city: Barcelona
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724002
city: Madrid
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724004
city: Málaga
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724001
city: Valencia
country: Spain
facility: Sanofi-Aventis Investigational Site Number 724003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.