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

NCT00314977 | Completed Phase 3

• 1 other identifier: IKO 2005-01 / BOOG 2007-02
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 24

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.

Conditions

Breast Cancer

Keywords

Large resectable breast cancer; Locally advanced breast cancer; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• The pathologic complete response rate to neoadjuvant chemotherapy.

Secondary Outcomes (9)

• 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.

Study Arms (2)

A

EXPERIMENTAL

Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel

B

EXPERIMENTAL

Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

Doxorubicin DRUG

doxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2)

Also known as: hydroxyldaunorubicin, adriamycin

A; B

Cyclophosphamide DRUG

Cyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2)

Also known as: Cytoxan, Neosar, Revimmune

A; B

Docetaxel DRUG

Docetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2)

Also known as: Taxotere

A; B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Sanofi: collaborator
• Amgen: collaborator

Study Sites (24)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Slingeland Hospital

Doetinchem, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

St. Anna Hospital

Geldrop, Netherlands

Location

St. Jansdal Ziekenhuis

Harderwijk, Netherlands

Location

Atrium Medisch Centrum

Heerlen, Netherlands

Location

Elkerliek Ziekenhuis

Helmond, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, Netherlands

Location

Academical Hospital Maastricht (AZM)

Maastricht, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

Location

Radboud University Medical Centre

Nijmegen, Netherlands

Location

Waterland Hospital

Purmerend, Netherlands

Location

Maasland Hospital

Sittard, Netherlands

Location

HAGA Ziekenhuis

The Hague, Netherlands

Location

St. Elisabeth Ziekenhuis

Tilburg, Netherlands

Location

Mesos Medisch Centrum

Utrecht, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

Maxima Medisch Centrum

Veldhoven, Netherlands

Location

Zaans Medical Centre

Zaandam, Netherlands

Location

Related Publications (2)

• Vriens BEPJ, Vriens IJH, Aarts MJB, van Gastel SM, van den Berkmortel FWPJ, Smilde TJ, van Warmerdam LJC, van Spronsen DJ, Peer PGM, de Boer M, Tjan-Heijnen VCG; Breast Cancer Trialists' Group of the Netherlands (BOOG). Improved survival for sequentially as opposed to concurrently delivered neoadjuvant chemotherapy in non-metastatic breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):593-600. doi: 10.1007/s10549-017-4364-8. Epub 2017 Jul 3.

  PMID: 28674765 DERIVED

• Vriens BE, de Vries B, Lobbes MB, van Gastel SM, van den Berkmortel FW, Smilde TJ, van Warmerdam LJ, de Boer M, van Spronsen DJ, Smidt ML, Peer PG, Aarts MJ, Tjan-Heijnen VC; INTENS Study Group. Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer. Eur J Cancer. 2016 Jan;52:67-76. doi: 10.1016/j.ejca.2015.10.010. Epub 2015 Nov 30.

  PMID: 26650831 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• V.C.G. Tjan-Heijnen

  AZM Maastricht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 14, 2006
• First Posted: April 17, 2006
• Study Start: February 1, 2006
• Primary Completion: April 1, 2009
• Last Updated: March 18, 2010

Record last verified: 2010-03

Locations

NL (24)