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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01204125
First received: September 13, 2010
Last updated: September 14, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer Female
Drug: paclitaxel
Drug: Iniparib (SAR2405550 -BSI-201)
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: Randomized, Open-label, Phase 2 Study of the Efficacy and Safety of Weekly Paclitaxel Single-agent and Two Different Regimens of the PARP-1 Inhibitor SAR240550 (BSI-201) in Combination With Weekly Paclitaxel, as Neoadjuvant Therapy in Patients With Stage II-IIIA Triple Negative Breast Cancer (TNBC)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 [ Time Frame: at the time of definitive surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathological Complete Response (pCR) rate in the breast and axilla [ Time Frame: at the time of definitive surgery ] [ Designated as safety issue: No ]
  • Objective Response Rate(ORR) defined in the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as complete response rate + partial response rate [ Time Frame: at the time of definitive surgery ] [ Designated as safety issue: No ]
  • Breast conservation rate [ Time Frame: at the time of definitive surgery ] [ Designated as safety issue: No ]
  • Disease Free Survival rate (DFS) [ Time Frame: up to a maximum of 5 years after definitive surgery ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: up to a maximum of 5 years after definitive surgery ] [ Designated as safety issue: No ]
  • Safety parameters (number of patients AE, SAE or AEPM) [ Time Frame: up to a maximum of 5 years after definitive surgery ] [ Designated as safety issue: Yes ]
  • Molecular-biological testing [ Time Frame: 2 or 3 timepoints during treatment period ] [ Designated as safety issue: No ]

Estimated Enrollment: 141
Study Start Date: September 2010
Estimated Study Completion Date: February 2017
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: Iniparib (SAR2405550 -BSI-201)

Pharmaceutical form : solution for infusion

Route of administration :Intravenous

Experimental: 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).
Drug: Iniparib (SAR2405550 -BSI-201)

Pharmaceutical form : solution for infusion

Route of administration :Intravenous

Active Comparator: 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.
Drug: paclitaxel

Pharmaceutical form:solution for infusion

Route of administration: intravenous


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.

  Eligibility

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

  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: NCT01204125

Locations
France
Investigational Site Number 250001
Besancon Cedex, France, 25030
Investigational Site Number 250004
Bordeaux, France, 33076
Investigational Site Number 250006
Bron Cedex, France, 69677
Investigational Site Number 250003
Paris Cedex 10, France, 75475
Investigational Site Number 250002
Toulouse, France, 31052
Investigational Site Number 250005
Villejuif, France, 94805
Germany
Investigational Site Number 276003
Erlangen, Germany, 91054
Investigational Site Number 276004
Hamburg, Germany, 20357
Investigational Site Number 276002
Köln, Germany, 50931
Investigational Site Number 276001
Mönchengladbach, Germany, 41061
Spain
Investigational Site Number 724001
Barcelona, Spain, 08035
Investigational Site Number 724009
Cáceres, Spain, 10003
Investigational Site Number 724013
Córdoba, Spain, 14004
Investigational Site Number 724006
Islas Baleares, Spain, 07014
Investigational Site Number 724012
Jaén, Spain, 23007
Investigational Site Number 724002
Lérida, Spain, 25198
Investigational Site Number 724016
Madrid, Spain, 28041
Investigational Site Number 724005
Madrid, Spain, 28033
Investigational Site Number 724007
Reus, Spain, 43201
Investigational Site Number 724018
Santiago De Compostela, Spain, 15706
Investigational Site Number 724010
Sevilla, Spain, 41013
Investigational Site Number 724017
Sevilla, Spain, 41009
Investigational Site Number 724003
Torrevieja, Spain, 03186
Investigational Site Number 724011
Valencia, Spain, 46009
Investigational Site Number 724015
Valencia, Spain, 46010
Sponsors and Collaborators
Sanofi
SOLTI Breast Cancer Research Group
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01204125     History of Changes
Other Study ID Numbers: TCD11419, 2010-018960-17
Study First Received: September 13, 2010
Last Updated: September 14, 2013
Health Authority: Spain: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014