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

Sponsor

AZ-VUB (Other)

Overall Status

Completed

CT.gov ID

NCT04224922

Collaborator

Universitaire Ziekenhuizen Leuven (Other), Universitair Ziekenhuis Brussel (Other)

Enrollment

Locations

Arm

Actual Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Paclitaxel Drug: Carboplatinum Drug: Epirubicin Drug: Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

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: Paclitaxel Drug: Carboplatinum Drug: Epirubicin Drug: Cyclophosphamide

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: Paclitaxel

Drug: Carboplatinum

Drug: Epirubicin

Drug: Cyclophosphamide

Outcome Measures

Primary Outcome Measures

-The rate of pCR in the breast and axilla (ypT0/is, ypN0) [20 weeks]

Secondary Outcome Measures

Evaluation of tumor infiltrating lymphocytes on the residual tumor [20 weeks]
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 [20 weeks]
Evaluation of the drug delivery [20 weeks]
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. [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 [20 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Onze Lieve Vrouw Ziekenhuis	Aalst	Belgium	9300
2	Cliniques Sud Luxembourg	Arlon	Belgium	6700
3	Imelda Ziekenhuis	Bonheiden	Belgium	2820
4	AZ klina	Brasschaat	Belgium	2930
5	St Lucas	Brugge	Belgium	8310
6	Institut Jules Bordet	Brussels	Belgium	1000
7	Universitaire Ziekenhuis Antwerpen	Edegem	Belgium	2650
8	AZ Maria Middelares	Gent	Belgium	9000
9	AZ St Lucas	Gent	Belgium	9000
10	AZ Groeninge	Kortrijk	Belgium	8500
11	UZ Leuven	Leuven	Belgium	3000
12	CHR Citadelle	Liège	Belgium	4000
13	CHU Sart-Tilman	Liège	Belgium	4000
14	CMSE	Namur	Belgium	5000
15	Clinique st Pierre	Ottignies	Belgium	1340
16	CHWAPI	Tournai	Belgium	7500
17	CHR Verviers	Verviers	Belgium	4800
18	CHU Mont-Godinne	Yvoir	Belgium	5530