Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable or Locally Advanced Breast Cancer.

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel

• Registration Number: NCT00314977
• Lead Sponsor: Radboud University Medical Center

Brief Summary

2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. The aim of the study is to compare the efficacy and tolerability of neoadjuvant chemotherapy with AC followed by T(adriamycin, cyclophosphamide, taxotere) versus TAC ( with upfront T) in patient with large resectable or locally advanced breast cancer.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2006-04-14
• Study First Submitted QC: 2006-04-14
• Study First Posted: 2006-04-17
• Primary Completion: 2009-04
• Status Verified: 2010-03
• Last Update Submitted: 2010-03-17
• Last Update Posted: 2010-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 200

Inclusion Criteria

• Women presenting with large resectable or locally advanced breast cancer (T2 ≥3 cm, T3, or T4, and/or LN positive)
• Measurable disease (breast and/or lymph nodes)
• No prior surgery other than biopsy and no prior chemotherapy or radiation therapy
• Age ≥18 years and age ≤70 years
• Karnofsky Performance score ≥70%
• Estrogen and/or progesterone receptor analysis performed on the primary tumour in the biopsy material
• In case the tumor is ER/PgR ³ 50% positive, (neo)adjuvant hormonal therapy in stead of chemotherapy should be considered (e.g. in TEAM II study)
• Her2/neu receptor analysis performed on the primary tumour in the biopsy material
• Adequate bone marrow function (within 14 days prior to registration): WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function (within 4 weeks prior to start treatment): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function (within 4 weeks prior to start treatment): the calculated creatinine clearance should be ≥50 mL/min
• Patients must be accessible for treatment and follow-up
• Written informed consent according to the local Ethics Committee requirements

Exclusion Criteria

• Patients with advanced pulmonary disease of any cause (oxygen dependent)- Peripheral neuropathy > grade 2 whatever the cause
• Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrythmias
• Evidence of distant metastases (M1)
• Patients with a history of breast cancer
• Patients with a history of another malignancy (except basal cell skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry- Pregnant or lactating women, or potentially fertile women not using adequate contraception

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Doxorubicin	Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel
A	Cyclophosphamide	Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel
A	Docetaxel	Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel
B	Doxorubicin	Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel
B	Docetaxel	Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel
B	Cyclophosphamide	Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel

Primary Outcome Measures

Name	Time	Method
The pathologic complete response rate to neoadjuvant chemotherapy.

Secondary Outcome Measures

Name	Time	Method
The delivered chemotherapy dose and dose-intensity of both chemotherapy regimens
The tolerability (grade 3/4 CTC toxicities) of both chemotherapy regimens.
The clinical responses of neoadjuvant chemotherapy correlated to pathological responses after neoadjuvant chemotherapy.
The value of breast MRI in evaluating response to neoadjuvant chemotherapy as compared to clinical palpation, ultrasound techniques and histo-pathological outcome.
The false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy.
The disease-free and overall survival after 3 and 5 years follow-up.
The relation between pCR and DFS/OS.
The feasibility of the criteria for reporting pathological tumour response in surgical breast and axillary node resection specimens.
The prognostic and predictive value of tumour- and molecular markers, including ER, PgR, c-erbB2, microarray and other tumour characteristic analyses.

Trial Locations

Locations (24)

Jeroen Bosch Ziekenhuis; 🇳🇱 Den Bosch, Netherlands

Deventer Ziekenhuis; 🇳🇱 Deventer, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

HAGA Ziekenhuis; 🇳🇱 Den Haag, Netherlands

Maasland Hospital; 🇳🇱 Sittard, Netherlands

Canisius Wilhelmina Ziekenhuis; 🇳🇱 Nijmegen, Netherlands

Maxima Medisch Centrum; 🇳🇱 Veldhoven, Netherlands

Onze Lieve Vrouwe Gasthuis; 🇳🇱 Amsterdam, Netherlands

Rijnstate Ziekenhuis; 🇳🇱 Arnhem, Netherlands

Mesos Medisch Centrum; 🇳🇱 Utrecht, Netherlands

Leids Universitair Medisch Centrum (LUMC); 🇳🇱 Leiden, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

Atrium Medisch Centrum; 🇳🇱 Heerlen, Netherlands

Elkerliek Ziekenhuis; 🇳🇱 Helmond, Netherlands

Spaarne Ziekenhuis; 🇳🇱 Hoofddorp, Netherlands

St. Antonius Hospital; 🇳🇱 Nieuwegein, Netherlands

Slingeland Hospital; 🇳🇱 Doetinchem, Netherlands

St. Anna Hospital; 🇳🇱 Geldrop, Netherlands

St. Jansdal Ziekenhuis; 🇳🇱 Harderwijk, Netherlands

Radboud University Medical Centre; 🇳🇱 Nijmegen, Netherlands

Waterland Hospital; 🇳🇱 Purmerend, Netherlands

St. Elisabeth Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Zaans Medical Centre; 🇳🇱 Zaandam, Netherlands

Academical Hospital Maastricht (AZM); 🇳🇱 Maastricht, Netherlands