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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatinum

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Onze Lieve Vrouw Ziekenhuis
  • Arlon, Belgium, 6700
    • Cliniques Sud Luxembourg
  • Bonheiden, Belgium, 2820
    • Imelda Ziekenhuis
  • Brasschaat, Belgium, 2930
    • AZ Klina
  • Brugge, Belgium, 8310
    • St Lucas
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Universitaire Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • AZ Maria Middelares
  • Gent, Belgium, 9000
    • AZ St Lucas
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Liège, Belgium, 4000
    • CHR Citadelle
  • Namur, Belgium, 5000
    • CMSE
  • Ottignies, Belgium, 1340
    • Clinique St Pierre
  • Tournai, Belgium, 7500
    • CHwapi
  • Verviers, Belgium, 4800
    • CHR Verviers
  • Yvoir, Belgium, 5530
    • CHU Mont-Godinne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single-arm; 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	Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
-The rate of pCR in the breast and axilla (ypT0/is, ypN0)	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	20 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03		20 weeks
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	20 weeks
Evaluation of clinical response rate (RECIST 1.1) by mammography and sonography in breast and axilla.		20 weeks
Evaluation of breast-conserving surgery rate		20 weeks
Evaluation of progression free survival		20 weeks
Evaluation of overall survival		20 weeks
Evaluation of percentage of patients with BRCA1 or BRCA2 in this population.		20 weeks
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.	20 weeks

Collaborators and Investigators

• Sponsor: AZ-VUB
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Christel Fontaine, Dr., Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Carboplatin; Paclitaxel; Epirubicin
• Other Study ID Numbers: BSMO-2014-01