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

NCT01204125 | Completed Phase 2

• 2 other identifiers: TCD114192010-018960-17
• Study Type: interventional
• Target: 141
• Locations: 3 countries
• Sites: 25

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.

Conditions

Breast Cancer Female

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) rate defined as the complete absence of invasive carcinoma on histological examination of the breast at the time of definitive surgery and confirmed by blinded centralized review

  at the time of definitive surgery

Secondary Outcomes (7)

• Pathological Complete Response (pCR) rate in the breast and axilla

  at the time of definitive surgery

• Objective Response Rate(ORR) defined in the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as complete response rate + partial response rate

  at the time of definitive surgery

• Breast conservation rate

  at the time of definitive surgery

• Disease Free Survival rate (DFS)

  up to a maximum of 5 years after definitive surgery

• Overall Survival (OS)

  up to a maximum of 5 years after definitive surgery

Study Arms (3)

SAR240550 twice weekly/ paclitaxel weekly

EXPERIMENTAL

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).

Drug: Iniparib (SAR2405550 -BSI-201)

SAR240550 weekly/ paclitaxel weekly

EXPERIMENTAL

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).

Drug: Iniparib (SAR2405550 -BSI-201)

Paclitaxel alone

ACTIVE COMPARATOR

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

Drug: paclitaxel

Interventions

paclitaxel DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Paclitaxel alone

Iniparib (SAR2405550 -BSI-201) DRUG

Pharmaceutical form : solution for infusion Route of administration :Intravenous

SAR240550 twice weekly/ paclitaxel weekly; SAR240550 weekly/ paclitaxel weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• SOLTI Breast Cancer Research Group: collaborator

Study Sites (25)

Investigational Site Number 250001

Besançon, 25030, France

Location

Investigational Site Number 250004

Bordeaux, 33076, France

Location

Investigational Site Number 250006

Bron, 69677, France

Location

Investigational Site Number 250003

Paris, 75475, France

Location

Investigational Site Number 250002

Toulouse, 31052, France

Location

Investigational Site Number 250005

Villejuif, 94805, France

Location

Investigational Site Number 276002

Cologne, 50931, Germany

Location

Investigational Site Number 276003

Erlangen, 91054, Germany

Location

Investigational Site Number 276004

Hamburg, 20357, Germany

Location

Investigational Site Number 276001

Mönchengladbach, 41061, Germany

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Investigational Site Number 724009

Cáceres, 10003, Spain

Location

Investigational Site Number 724013

Córdoba, 14004, Spain

Location

Investigational Site Number 724006

Islas Baleares, 07014, Spain

Location

Investigational Site Number 724012

Jaén, 23007, Spain

Location

Investigational Site Number 724002

Lleida, 25198, Spain

Location

Investigational Site Number 724005

Madrid, 28033, Spain

Location

Investigational Site Number 724016

Madrid, 28041, Spain

Location

Investigational Site Number 724007

Reus, 43201, Spain

Location

Investigational Site Number 724018

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 724017

Seville, 41009, Spain

Location

Investigational Site Number 724010

Seville, 41013, Spain

Location

Investigational Site Number 724003

Torrevieja, 03186, Spain

Location

Investigational Site Number 724011

Valencia, 46009, Spain

Location

Investigational Site Number 724015

Valencia, 46010, Spain

Location

Related Publications (1)

• 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.

  PMID: 26536871 DERIVED

MeSH Terms

Interventions

Paclitaxel; iniparib

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 17, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: February 1, 2017
• Last Updated: March 22, 2017

Record last verified: 2017-03

Locations

ES (15); DE (4); FR (6)