Clinical trial NCT00314977: Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable or Locally Advanced Breast Cancer.
Official title: Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Large resectable breast cancer
Locally advanced breast cancer
Neoadjuvant therapy
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Amgen
First posted: 2006-04-17
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The pathologic complete response rate to neoadjuvant chemotherapy.
Secondary outcomes:
measure: The delivered chemotherapy dose and dose-intensity of both chemotherapy regimens
measure: The tolerability (grade 3/4 CTC toxicities) of both chemotherapy regimens.
measure: The clinical responses of neoadjuvant chemotherapy correlated to pathological responses after neoadjuvant chemotherapy.
measure: The value of breast MRI in evaluating response to neoadjuvant chemotherapy as compared to clinical palpation, ultrasound techniques and histo-pathological outcome.
measure: The false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy.
measure: The disease-free and overall survival after 3 and 5 years follow-up.
measure: The relation between pCR and DFS/OS.
measure: The feasibility of the criteria for reporting pathological tumour response in surgical breast and axillary node resection specimens.
measure: The prognostic and predictive value of tumour- and molecular markers, including ER, PgR, c-erbB2, microarray and other tumour characteristic analyses.
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Den Haag
country: Netherlands
facility: HAGA Ziekenhuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Doetinchem
country: Netherlands
facility: Slingeland Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Geldrop
country: Netherlands
facility: St. Anna Hospital
city: Harderwijk
country: Netherlands
facility: St. Jansdal Ziekenhuis
city: Heerlen
country: Netherlands
facility: Atrium Medisch Centrum
city: Helmond
country: Netherlands
facility: Elkerliek Ziekenhuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC)
city: Maastricht
country: Netherlands
facility: Academical Hospital Maastricht (AZM)
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
city: Purmerend
country: Netherlands
facility: Waterland Hospital
city: Sittard
country: Netherlands
facility: Maasland Hospital
city: Tilburg
country: Netherlands
facility: St. Elisabeth Ziekenhuis
city: Utrecht
country: Netherlands
facility: Mesos Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Zaandam
country: Netherlands
facility: Zaans Medical Centre
Study officials:
affiliation: AZM Maastricht
name: V.C.G. Tjan-Heijnen
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.