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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04224922
• Other study ID #: BSMO-2014-01
• Status: Completed
• Phase: Phase 2
• Start date: May 2015
• Est. completion date: May 2017

Study information

• Verified date: January 2020
• Source: AZ-VUB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: May 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Paclitaxel

• Carboplatinum

• Epirubicin

• Cyclophosphamide

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouw Ziekenhuis	Aalst
Belgium	Cliniques Sud Luxembourg	Arlon
Belgium	Imelda Ziekenhuis	Bonheiden
Belgium	AZ klina	Brasschaat
Belgium	St Lucas	Brugge
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitaire Ziekenhuis Antwerpen	Edegem
Belgium	AZ Maria Middelares	Gent
Belgium	AZ St Lucas	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CHR Citadelle	Liège
Belgium	CHU Sart-Tilman	Liège
Belgium	CMSE	Namur
Belgium	Clinique st Pierre	Ottignies
Belgium	CHWAPI	Tournai
Belgium	CHR Verviers	Verviers
Belgium	CHU Mont-Godinne	Yvoir

Sponsors (3)

Lead Sponsor	Collaborator
AZ-VUB	Universitair Ziekenhuis Brussel, Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	-The rate of pCR in the breast and axilla (ypT0/is, ypN0)		20 weeks
Secondary	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
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03		20 weeks
Secondary	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
Secondary	Evaluation of clinical response rate (RECIST 1.1) by mammography and sonography in breast and axilla.		20 weeks
Secondary	Evaluation of breast-conserving surgery rate		20 weeks
Secondary	Evaluation of progression free survival		20 weeks
Secondary	Evaluation of overall survival		20 weeks
Secondary	Evaluation of percentage of patients with BRCA1 or BRCA2 in this population.		20 weeks
Secondary	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