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

Primary Purpose

Breast Cancer Female

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
paclitaxel
Iniparib (SAR2405550 -BSI-201)
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer Female

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 250001
  • Investigational Site Number 250004
  • Investigational Site Number 250006
  • Investigational Site Number 250003
  • Investigational Site Number 250002
  • Investigational Site Number 250005
  • Investigational Site Number 276003
  • Investigational Site Number 276004
  • Investigational Site Number 276002
  • Investigational Site Number 276001
  • Investigational Site Number 724001
  • Investigational Site Number 724009
  • Investigational Site Number 724013
  • Investigational Site Number 724006
  • Investigational Site Number 724012
  • Investigational Site Number 724002
  • Investigational Site Number 724005
  • Investigational Site Number 724016
  • Investigational Site Number 724007
  • Investigational Site Number 724018
  • Investigational Site Number 724017
  • Investigational Site Number 724010
  • Investigational Site Number 724003
  • Investigational Site Number 724011
  • Investigational Site Number 724015

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

SAR240550 twice weekly/ paclitaxel weekly

SAR240550 weekly/ paclitaxel weekly

Paclitaxel alone

Arm Description

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).

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).

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

Outcomes

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

Secondary Outcome Measures

Pathological Complete Response (pCR) rate in the breast and axilla
Objective Response Rate(ORR) defined in the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as complete response rate + partial response rate
Breast conservation rate
Disease Free Survival rate (DFS)
Overall Survival (OS)
Safety parameters (number of patients AE, SAE or AEPM)
Molecular-biological testing

Full Information

First Posted
September 13, 2010
Last Updated
March 21, 2017
Sponsor
Sanofi
Collaborators
SOLTI Breast Cancer Research Group
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1. Study Identification

Unique Protocol Identification Number
NCT01204125
Brief Title
Two Regimens of SAR240550/Weekly Paclitaxel and Paclitaxel Alone as Neoadjuvant Therapy in Triple Negative Breast Cancer Patients
Acronym
SOLTI NEOPARP
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
February 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
SOLTI Breast Cancer Research Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer Female

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
141 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR240550 twice weekly/ paclitaxel weekly
Arm Type
Experimental
Arm Description
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).
Arm Title
SAR240550 weekly/ paclitaxel weekly
Arm Type
Experimental
Arm Description
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).
Arm Title
Paclitaxel alone
Arm Type
Active Comparator
Arm Description
Paclitaxel will be administered at the dose of 80mg/m2 as a 60-min IV infusion. Patients will receive weekly (day 1) paclitaxel infusions.
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
Pharmaceutical form:solution for infusion Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
Iniparib (SAR2405550 -BSI-201)
Intervention Description
Pharmaceutical form : solution for infusion Route of administration :Intravenous
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Pathological Complete Response (pCR) rate in the breast and axilla
Time Frame
at the time of definitive surgery
Title
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
Title
Breast conservation rate
Time Frame
at the time of definitive surgery
Title
Disease Free Survival rate (DFS)
Time Frame
up to a maximum of 5 years after definitive surgery
Title
Overall Survival (OS)
Time Frame
up to a maximum of 5 years after definitive surgery
Title
Safety parameters (number of patients AE, SAE or AEPM)
Time Frame
up to a maximum of 5 years after definitive surgery
Title
Molecular-biological testing
Time Frame
2 or 3 timepoints during treatment period

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 250001
City
Besancon Cedex
ZIP/Postal Code
25030
Country
France
Facility Name
Investigational Site Number 250004
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Investigational Site Number 250006
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Investigational Site Number 250003
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Investigational Site Number 250002
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
Investigational Site Number 250005
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Investigational Site Number 276003
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Investigational Site Number 276004
City
Hamburg
ZIP/Postal Code
20357
Country
Germany
Facility Name
Investigational Site Number 276002
City
Köln
ZIP/Postal Code
50931
Country
Germany
Facility Name
Investigational Site Number 276001
City
Mönchengladbach
ZIP/Postal Code
41061
Country
Germany
Facility Name
Investigational Site Number 724001
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number 724009
City
Cáceres
ZIP/Postal Code
10003
Country
Spain
Facility Name
Investigational Site Number 724013
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Investigational Site Number 724006
City
Islas Baleares
ZIP/Postal Code
07014
Country
Spain
Facility Name
Investigational Site Number 724012
City
Jaén
ZIP/Postal Code
23007
Country
Spain
Facility Name
Investigational Site Number 724002
City
Lérida
ZIP/Postal Code
25198
Country
Spain
Facility Name
Investigational Site Number 724005
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Investigational Site Number 724016
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigational Site Number 724007
City
Reus
ZIP/Postal Code
43201
Country
Spain
Facility Name
Investigational Site Number 724018
City
Santiago De Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Investigational Site Number 724017
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Investigational Site Number 724010
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Investigational Site Number 724003
City
Torrevieja
ZIP/Postal Code
03186
Country
Spain
Facility Name
Investigational Site Number 724011
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Investigational Site Number 724015
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
26536871
Citation
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.
Results Reference
derived

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

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