Two Regimens of SAR240550/Weekly Paclitaxel and Paclitaxel Alone as Neoadjuvant Therapy in Triple Negative Breast Cancer Patients

NCT ID: NCT01204125

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2017-02-28

Brief Summary

Primary Objective:

• to assess the pathological Complete Response (pCR) rate in the breast of patients treated in following combinations: SAR240550 twice-weekly + weekly paclitaxel, SAR240550 weekly+ weekly paclitaxel, and weekly paclitaxel single agent as calibrator.

Secondary objectives are:

• pCR rate in the breast and axilla,
• Radiological/clinical objective response rate (ORR), breast conservation rate, disease free survival (DFS), and overall survival (OS), in each treatment arm,
• Safety profiles of study combinations and of the single agent reference treatment,
• Molecular characteristics of the tumor tissue and peripheral blood mononuclear cells (PBMC) and any correlation between the biological activity of the study treatment and the disease outcome.

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

Detailed Description

Active study treatment will be given either as twice weekly administration (Day 1 and Day 4) or as weekly administration (Day 1) for a maximum of 24 infusions for Arm A and for a maximum of 12 infusions for Arm B. In all study arms, treatment will be given until definitive surgery, the first sign of disease progression, unacceptable toxicity or withdrawal of patient consent.

Definitive surgery will be performed within 2 to 4 weeks after the last dose of study treatment.

Patients who complete all the study treatment or who withdraw consent or experience intolerable toxicity will undergo surgery according to local practices.

The cut-off date for the primary analyses will be 30 days after the last study treatment administration or the date of the definitive surgery, whichever comes last.

The maximum follow up for each individual patient will be until death or 5 years after the definitive surgery date whatever happens first.

Conditions

Breast Cancer Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR240550 twice weekly/ paclitaxel weekly

SAR240550 will be administered at the dose of 5.6mg/kg as a 60-min intravenous (IV) infusion. Patients will receive SAR240550 infusions twice weekly (day 1 and day 4; total dose of 11.2mg/kg per week) and paclitaxel weekly as a 60-min IV infusion (day 1; dose of 80mg/m2).

Group Type: EXPERIMENTAL

Iniparib (SAR2405550 -BSI-201)

Intervention Type: DRUG

Pharmaceutical form : solution for infusion

Route of administration :Intravenous

SAR240550 weekly/ paclitaxel weekly

SAR240550 will be administered at the dose of 11.2 mg/kg as a 60-min intravenous (IV) infusion. Patients will receive SAR240550 infusions once weekly (day 1; total dose of 11.2mg/kg per week) and paclitaxel weekly as a 60-min IV infusion (day 1; dose of 80mg/m2).

Group Type: EXPERIMENTAL

Iniparib (SAR2405550 -BSI-201)

Intervention Type: DRUG

Pharmaceutical form : solution for infusion

Route of administration :Intravenous

Paclitaxel alone

Paclitaxel will be administered at the dose of 80mg/m2 as a 60-min IV infusion. Patients will receive weekly (day 1) paclitaxel infusions.

Group Type: ACTIVE_COMPARATOR

paclitaxel

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Interventions

paclitaxel

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

Iniparib (SAR2405550 -BSI-201)

Pharmaceutical form : solution for infusion

Route of administration :Intravenous

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed Stage II-IIIA invasive breast cancer eligible for definitive surgery and Estrogen Receptor (ER)-negative, Progesterone receptor (PgR)-negative and Human epidermal growth factor receptor 2 (HER2) non-overexpressing by Immunohistochemistry (IHC) (0+, 1+) or fluorescence in situ hybridization (FISH negative, ratio <1.8) or IHC (2+, 3+) /FISH-negative.
• The primary tumor must be > 2cm in diameter measured by physical examination and mammography (mandatory) plus either echography or Magnetic Resonance Imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate bone marrow reserve
• Adequate liver and renal function.
• Age > or = 18 years

Exclusion Criteria

• Any prior treatment for primary breast cancer.
• Bilateral or multicentric breast cancer.
• Other primary tumors within the previous 5 years, except for adequately controlled limited basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Pre-existing peripheral neuropathy grade > or = 2 as per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) at randomization.
• Any history of medical (e.g., cardiovascular, uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results
• Pregnancy or breastfeeding women.
• Women of childbearing potential (<2 years after the last menstruation) not using effective, non-hormonal means of contraception during the study and for a period of 6 months following the last administration of study drug.
• Requirement for radiation therapy concurrent with study anticancer treatment. Patients who require breast or chest wall radiation therapy after surgery are eligible.
• Known hypersensitivity to any of the study drugs or excipients

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

SOLTI Breast Cancer Research Group

OTHER

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 250001

Besançon, , France

Investigational Site Number 250004

Bordeaux, , France

Investigational Site Number 250006

Bron, , France

Investigational Site Number 250003

Paris, , France

Investigational Site Number 250002

Toulouse, , France

Investigational Site Number 250005

Villejuif, , France

Investigational Site Number 276002

Cologne, , Germany

Investigational Site Number 276003

Erlangen, , Germany

Investigational Site Number 276004

Hamburg, , Germany

Investigational Site Number 276001

Mönchengladbach, , Germany

Investigational Site Number 724001

Barcelona, , Spain

Investigational Site Number 724009

Cáceres, , Spain

Investigational Site Number 724013

Córdoba, , Spain

Investigational Site Number 724006

Islas Baleares, , Spain

Investigational Site Number 724012

Jaén, , Spain

Investigational Site Number 724002

Lleida, , Spain

Investigational Site Number 724005

Madrid, , Spain

Investigational Site Number 724016

Madrid, , Spain

Investigational Site Number 724007

Reus, , Spain

Investigational Site Number 724018

Santiago de Compostela, , Spain

Investigational Site Number 724017

Seville, , Spain

Investigational Site Number 724010

Seville, , Spain

Investigational Site Number 724003

Torrevieja, , Spain

Investigational Site Number 724011

Valencia, , Spain

Investigational Site Number 724015

Valencia, , Spain

Countries

France; Germany; Spain

References

Llombart-Cussac A, Bermejo B, Villanueva C, Delaloge S, Morales S, Balmana J, Amillano K, Bonnefoi H, Casas A, Manso L, Roche H, Gonzalez-Santiago S, Gavila J, Sanchez-Rovira P, Di Cosimo S, Harbeck N, Charpentier E, Garcia-Ribas I, Radosevic-Robin N, Aura C, Baselga J. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer. Breast Cancer Res Treat. 2015 Nov;154(2):351-7. doi: 10.1007/s10549-015-3616-8. Epub 2015 Nov 4.

Reference Type: DERIVED

PMID: 26536871 (View on PubMed)

Other Identifiers

2010-018960-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TCD11419

Identifier Type: -

Identifier Source: org_study_id