search
Back to results

Phase II Study of Neoadjuvant Weekly Paclitaxel and Carboplatin Followed by Dose Dense Epirubicin and Cyclophosphamide in Stage II and III Triple Negative Breast Cancer

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Paclitaxel
Carboplatinum
Epirubicin
Cyclophosphamide
Sponsored by
AZ-VUB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Stage II-III operable triple negative (ER and PR < 10%; Her2 IHC 0-1 or FISH <2.0) breast cancer in women age > 18. For patients aged 65 or older the G8 geriatric screening test should be > 14 (on a total of 17).
  • Baseline mammography, US. MR of the breast on clinical indication.
  • FNA of suspicious axillary lymph node is indicated
  • Pre-treatment SN biopsy is indicated in clinical N0
  • Measurable loco-regional disease

  • Adequate bone marrow function, defined as

    • Absolute neutrophil count(ANC) >1500*109/L
    • Platelet count >100.000*109/L

  • Adequate liver function defined as

    • Serum(total) bilirubin <1.5*upper limit of normal(ULN), unless the patient has documented Gilbert's Syndrome
    • AST and/or ALT <2.5*ULN
    • Alkaline phosphatase <2.5*ULN
  • Normal cardiac function measured by ultrasound with a left ventricular function > 55%
  • Creatinine clearance > 40 ml/min according to local laboratory standard (MDRD, CDK-epi, Cockroft-Gault, or other established formula to calculate renal function)

Exclusion Criteria:

  • T4d breast tumor
  • Bilateral breast cancer
  • Other invasive cancer in the past except for a localized squamous cell cancer or basal cell of the skin or an in situ squamous cell cancer of the cervix.
  • Pregnant or lactating patients

Sites / Locations

  • Onze Lieve Vrouw Ziekenhuis
  • Cliniques Sud Luxembourg
  • Imelda Ziekenhuis
  • AZ klina
  • St Lucas
  • Institut Jules Bordet
  • Universitaire Ziekenhuis Antwerpen
  • AZ Maria Middelares
  • AZ St Lucas
  • AZ Groeninge
  • UZ Leuven
  • CHR Citadelle
  • CHU Sart-Tilman
  • CMSE
  • Clinique st Pierre
  • CHWAPI
  • CHR Verviers
  • CHU Mont-Godinne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single-arm

Arm Description

weekly paclitaxel at a dose of 80mg/m² in combination with weekly carboplatin (AUC=2), for 12 weeks, followed by 4 cycles of dose dense epirubicin at a dose of 90 mg/m² and cyclophosphamide at a dose of 600 mg/m² every 2 weeks (plus Long acting GCSF at day 2) administrated preoperatively in locally advanced operable stage II and III triple negative breast cancer

Outcomes

Primary Outcome Measures

-The rate of pCR in the breast and axilla (ypT0/is, ypN0)

Secondary Outcome Measures

Evaluation of tumor infiltrating lymphocytes on the residual tumor
Histopathological analysis of the lymphocyte infiltrate is performed on hematoxylin and eosin- stained sections of the core biopsies and afterwords on the resection specimen after neoadjuvant chemotherapy. Ancillary techniques and immunohistochemistry have no additional value upon this date, and are not recommanded. The overall assessment has to be made for the whole tumor area, regardless of hot spots. All mononuclear cells including lymphocytes and plasma cells should be scored (granulocytes and other polymorphonuclear leukocytes are excluded). The quantitative assessment of other mononuclear cells such as dendritic cells and macrophages is currently not recommended. TILs should be reported for the intratumoral lymphocytes (as first proposed by Denkert in 2010). Stromal lymphocytes (Str-Ly) are defined as the percentage of tumor stroma area that contains a lymphocytic infiltrate without direct contact to tumor cells.
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03
Evaluation of the drug delivery
Patient compliance for paclitaxel and carboplatin and for epirubicin and cyclophosphamide will be assessed by the investigator and/or study personnel at each patient visit. To accurately determine the patient's drug exposure throughout the study, the following information must be reported on the Drug Administration Record CRF pages and in the source document. Planned dose administration, Actual total daily dose administrated, Regimen, Start and end date of drug administration, Dose change, Reason for dose change
Evaluation of clinical response rate (RECIST 1.1) by mammography and sonography in breast and axilla.
Evaluation of breast-conserving surgery rate
Evaluation of progression free survival
Evaluation of overall survival
Evaluation of percentage of patients with BRCA1 or BRCA2 in this population.
genome analysis on tissue samples
Tumor tissue samples (FFPE) for genetic research will be obtained from consenting patients both at screening and at surgery. Genome analysis will be performed on (1) DNA extracted from EDTA blood (10ml) collected at the start of the treatment and (2) on DNA extracted from FFPE tumor tissue collected before the start of the neoadjuvant chemotherapy and after surgery.

Full Information

First Posted
January 7, 2020
Last Updated
January 13, 2020
Sponsor
AZ-VUB
Collaborators
Universitaire Ziekenhuizen KU Leuven, Universitair Ziekenhuis Brussel
search

1. Study Identification

Unique Protocol Identification Number
NCT04224922
Brief Title
Phase II Study of Neoadjuvant Weekly Paclitaxel and Carboplatin Followed by Dose Dense Epirubicin and Cyclophosphamide in Stage II and III Triple Negative Breast Cancer
Official Title
A Prospective, Belgian Multi-center, Single-arm, Phase II Study of Neoadjuvant Weekly Paclitaxel and Carboplatin Followed by Dose Dense Epirubicin and Cyclophosphamide in Stage II and III Triple Negative Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
May 2015 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
AZ-VUB
Collaborators
Universitaire Ziekenhuizen KU Leuven, Universitair Ziekenhuis Brussel

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a prospective Belgian, multi-center, open-label, single-arm phase II study of weekly paclitaxel at a dose of 80mg/m² in combination with weekly carboplatin (AUC=2), for 12 weeks, followed by 4 cycles of dose dense epirubicin at a dose of 90 mg/m² and cyclophosphamide at a dose of 600 mg/m² every 2 weeks (plus Long acting GCSF at day 2) administrated preoperatively in locally advanced operable stage II and III triple negative breast cancer to evaluate tumor response in the breast and the axilla.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
single-arm
Arm Type
Experimental
Arm Description
weekly paclitaxel at a dose of 80mg/m² in combination with weekly carboplatin (AUC=2), for 12 weeks, followed by 4 cycles of dose dense epirubicin at a dose of 90 mg/m² and cyclophosphamide at a dose of 600 mg/m² every 2 weeks (plus Long acting GCSF at day 2) administrated preoperatively in locally advanced operable stage II and III triple negative breast cancer
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Type
Drug
Intervention Name(s)
Carboplatinum
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Primary Outcome Measure Information:
Title
-The rate of pCR in the breast and axilla (ypT0/is, ypN0)
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
Evaluation of tumor infiltrating lymphocytes on the residual tumor
Description
Histopathological analysis of the lymphocyte infiltrate is performed on hematoxylin and eosin- stained sections of the core biopsies and afterwords on the resection specimen after neoadjuvant chemotherapy. Ancillary techniques and immunohistochemistry have no additional value upon this date, and are not recommanded. The overall assessment has to be made for the whole tumor area, regardless of hot spots. All mononuclear cells including lymphocytes and plasma cells should be scored (granulocytes and other polymorphonuclear leukocytes are excluded). The quantitative assessment of other mononuclear cells such as dendritic cells and macrophages is currently not recommended. TILs should be reported for the intratumoral lymphocytes (as first proposed by Denkert in 2010). Stromal lymphocytes (Str-Ly) are defined as the percentage of tumor stroma area that contains a lymphocytic infiltrate without direct contact to tumor cells.
Time Frame
20 weeks
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03
Time Frame
20 weeks
Title
Evaluation of the drug delivery
Description
Patient compliance for paclitaxel and carboplatin and for epirubicin and cyclophosphamide will be assessed by the investigator and/or study personnel at each patient visit. To accurately determine the patient's drug exposure throughout the study, the following information must be reported on the Drug Administration Record CRF pages and in the source document. Planned dose administration, Actual total daily dose administrated, Regimen, Start and end date of drug administration, Dose change, Reason for dose change
Time Frame
20 weeks
Title
Evaluation of clinical response rate (RECIST 1.1) by mammography and sonography in breast and axilla.
Time Frame
20 weeks
Title
Evaluation of breast-conserving surgery rate
Time Frame
20 weeks
Title
Evaluation of progression free survival
Time Frame
20 weeks
Title
Evaluation of overall survival
Time Frame
20 weeks
Title
Evaluation of percentage of patients with BRCA1 or BRCA2 in this population.
Time Frame
20 weeks
Title
genome analysis on tissue samples
Description
Tumor tissue samples (FFPE) for genetic research will be obtained from consenting patients both at screening and at surgery. Genome analysis will be performed on (1) DNA extracted from EDTA blood (10ml) collected at the start of the treatment and (2) on DNA extracted from FFPE tumor tissue collected before the start of the neoadjuvant chemotherapy and after surgery.
Time Frame
20 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stage II-III operable triple negative (ER and PR < 10%; Her2 IHC 0-1 or FISH <2.0) breast cancer in women age > 18. For patients aged 65 or older the G8 geriatric screening test should be > 14 (on a total of 17). Baseline mammography, US. MR of the breast on clinical indication. FNA of suspicious axillary lymph node is indicated Pre-treatment SN biopsy is indicated in clinical N0 Measurable loco-regional disease Adequate bone marrow function, defined as Absolute neutrophil count(ANC) >1500*109/L Platelet count >100.000*109/L Adequate liver function defined as Serum(total) bilirubin <1.5*upper limit of normal(ULN), unless the patient has documented Gilbert's Syndrome AST and/or ALT <2.5*ULN Alkaline phosphatase <2.5*ULN Normal cardiac function measured by ultrasound with a left ventricular function > 55% Creatinine clearance > 40 ml/min according to local laboratory standard (MDRD, CDK-epi, Cockroft-Gault, or other established formula to calculate renal function) Exclusion Criteria: T4d breast tumor Bilateral breast cancer Other invasive cancer in the past except for a localized squamous cell cancer or basal cell of the skin or an in situ squamous cell cancer of the cervix. Pregnant or lactating patients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christel Fontaine, Dr.
Organizational Affiliation
Universitair Ziekenhuis Brussel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Onze Lieve Vrouw Ziekenhuis
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Cliniques Sud Luxembourg
City
Arlon
ZIP/Postal Code
6700
Country
Belgium
Facility Name
Imelda Ziekenhuis
City
Bonheiden
ZIP/Postal Code
2820
Country
Belgium
Facility Name
AZ klina
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
Facility Name
St Lucas
City
Brugge
ZIP/Postal Code
8310
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Universitaire Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
AZ Maria Middelares
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
AZ St Lucas
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHR Citadelle
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CHU Sart-Tilman
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CMSE
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
Clinique st Pierre
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Facility Name
CHWAPI
City
Tournai
ZIP/Postal Code
7500
Country
Belgium
Facility Name
CHR Verviers
City
Verviers
ZIP/Postal Code
4800
Country
Belgium
Facility Name
CHU Mont-Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium

12. IPD Sharing Statement

Learn more about this trial

Phase II Study of Neoadjuvant Weekly Paclitaxel and Carboplatin Followed by Dose Dense Epirubicin and Cyclophosphamide in Stage II and III Triple Negative Breast Cancer

We'll reach out to this number within 24 hrs