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

This study has been completed.
Sponsor:
Collaborators:
Sanofi
Amgen
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00314977
First received: April 14, 2006
Last updated: March 17, 2010
Last verified: March 2010
  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.


Condition Intervention Phase
Breast Cancer
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • The pathologic complete response rate to neoadjuvant chemotherapy.

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.

Estimated Enrollment: 200
Study Start Date: February 2006
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Cycles 1-4 q 3 weeks: doxorubicin plus cyclophosphamide Cycles 5-8 q 3 weeks: docetaxel
Drug: 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 Name: Taxotere
Experimental: B
Cycles 1-6 q 3 weeks: doxorubicin, cyclophosphamide and docetaxel
Drug: 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 Name: Taxotere

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00314977

Locations
Netherlands
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
Radboud University Medical Centre
Nijmegen, Netherlands
Canisius Wilhelmina Ziekenhuis
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
Sponsors and Collaborators
Radboud University
Sanofi
Amgen
Investigators
Principal Investigator: V.C.G. Tjan-Heijnen AZM Maastricht
  More Information

No publications provided

Responsible Party: Prof dr V.C.G. Tjan-Heijnen, Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT00314977     History of Changes
Other Study ID Numbers: IKO 2005-01 / BOOG 2007-02
Study First Received: April 14, 2006
Last Updated: March 17, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Large resectable breast cancer
Locally advanced breast cancer
Neoadjuvant therapy

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Docetaxel
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014