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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionBreast Cancer
InterventionDrug: Doxorubicin
Drug: Cyclophosphamide
Drug: Docetaxel
PhasePhase 3
SponsorRadboud University
Responsible PartyRadboud University
ClinicalTrials.gov IdentifierNCT00314977
First ReceivedApril 14, 2006
Last UpdatedMarch 17, 2010
Last verifiedMarch 2010

Tracking Information[ + expand ][ + ]

First Received DateApril 14, 2006
Last Updated DateMarch 17, 2010
Start DateFebruary 2006
Estimated Primary Completion DateNot Provided
Current Primary Outcome MeasuresThe pathologic complete response rate to neoadjuvant chemotherapy.
Current Secondary Outcome Measures
  • 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.

Descriptive Information[ + expand ][ + ]

Brief TitleSequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable or Locally Advanced Breast Cancer.
Official TitleSequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study
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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: Doxorubicin
doxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2)
Other Names:
  • hydroxyldaunorubicin
  • adriamycin
Drug: Cyclophosphamide
Cyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2)
Other Names:
  • Cytoxan
  • Neosar
  • Revimmune
Drug: Docetaxel
Docetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2)
Other Names:
Taxotere
Study Arm (s)
  • Experimental: A
    Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel
  • Experimental: B
    Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment200
Estimated Completion DateNot Provided
Estimated Primary Completion DateApril 2009
Eligibility Criteria
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesNetherlands

Administrative Information[ + expand ][ + ]

NCT Number NCT00314977
Other Study ID NumbersIKO 2005-01 / BOOG 2007-02
Has Data Monitoring CommitteeNo
Information Provided ByRadboud University
Study SponsorRadboud University
CollaboratorsSanofi
Amgen
Investigators Principal Investigator: V.C.G. Tjan-Heijnen AZM Maastricht
Verification DateMarch 2010

Locations[ + expand ][ + ]

Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
Rijnstate Ziekenhuis
Arnhem, Netherlands
Jeroen Bosch Ziekenhuis
Den Bosch, Netherlands
HAGA Ziekenhuis
Den Haag, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
Slingeland Hospital
Doetinchem, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
St. Anna Hospital
Geldrop, Netherlands
St. Jansdal Ziekenhuis
Harderwijk, Netherlands
Atrium Medisch Centrum
Heerlen, Netherlands
Elkerliek Ziekenhuis
Helmond, Netherlands
Spaarne Ziekenhuis
Hoofddorp, Netherlands
Leids Universitair Medisch Centrum (LUMC)
Leiden, Netherlands
Academical Hospital Maastricht (AZM)
Maastricht, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Radboud University Medical Centre
Nijmegen, Netherlands
Waterland Hospital
Purmerend, Netherlands
Maasland Hospital
Sittard, Netherlands
St. Elisabeth Ziekenhuis
Tilburg, Netherlands
Mesos Medisch Centrum
Utrecht, Netherlands
UMC Utrecht
Utrecht, Netherlands
Maxima Medisch Centrum
Veldhoven, Netherlands
Zaans Medical Centre
Zaandam, Netherlands