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

Breast Cancer Clinical Trial

— INTENS  

Official title:

Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00314977
• Other study ID #: IKO 2005-01 / BOOG 2007-02
• Status: Completed
• Phase: Phase 3
• First received: April 14, 2006
• Last updated: March 17, 2010
• Start date: February 2006

Study information

• Verified date: March 2010
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Doxorubicin
doxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2)
• Cyclophosphamide
Cyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2)
• Docetaxel
Docetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2)

Locations

Country	Name	City	State
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	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

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Amgen, Sanofi

Country where clinical trial is conducted

Netherlands, 

Outcome

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