Clinical trial NCT00425516: Breast Cancer Treated by Neoadjuvant Chemotherapy
Official title: Clinical Trial of the Neoadjuvant Standard Chemotherapy 3 FEC 100 + 3 TAXOTERE Protocol Versus the Same Protocol Adapted as a Function of Clinical Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Individualized Chemotherapy
Keywords: neoadjuvant chemotherapy
breast cancer
sequential treatment
Lead sponsor: Centre Jean Perrin
Sponsor class: OTHER
First posted: 2007-01-23
Enrollment: 264
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: Neoadjuvant chemotherapy, known as "first" or "induction chemotherapy" in the therapeutic assumption of breast cancer is based on the narrow dependence preclinically revealed between primary tumour, tumoral angiogenesis and growth of distant metastases.

The results of the Aberdeen Group (Smith et al, 2002 ; Hutcheon et al, 2003), of the NSABP B27 trial (Bear et al, 2003) and of the Gepar-Duo Group (Von Minckwitz et al, 2002) have shown that a sequential protocol, using docetaxel after an anthracycline-based combination, allowed a better clinical response leading to more frequent conservative surgeries and, more importantly, to an increase in the rate of complete pathological response, assessing a better efficacy.

The use of a reference adjuvant protocol as a neo-adjuvant treatment is fully admissible because 7 randomized trials have shown a perfect equivalence between an adjuvant protocol and the same chemotherapy given as an induction treatment Even keeping the principle of a sequential treatment, a crucial question is to know if this sequential treatment should be the same for all patients, or if the oncologist could get a better complete pathological response, disease-free or overall survival rates by an adaptation of treatment to the objective result beginning after 2 FEC 100 courses by modulation of the following courses.

We will use as a primary regimen 3 FEC cycles + 3 TAXOTERE cycles, a standard adjuvant regimen (noted in the Temporary Protocol of Treatment of the Inca page 5 (October 2005) as well as in Saint Paul de Vence 2005 recommendations for adjuvant chemotherapy (Oncologie -- volume 7 - N°5, August 2005, p 370). This standard treatment will be compared to the same chemotherapy modulated in its repartition according to results obtained by subsequent tumor evaluations during induction therapy.


Eligibility criteria: Inclusion Criteria:

* Patient with histological proof of non metastatic breast cancer, whose clinical tumor diameter is \> 2 cm, or \< 2 cm, but situated in areolar area of the nipple.
* T2-T3, N0-N1 tumor, non-inflammatory, unilateral, non-metastatic, grade II - III, HER2-neu negative, without extension beyond the breast and axillar area.
* Performance Status = 0-1 WHO.
* Patient non pretreated for breast cancer.
* Patient without cardiac pathology and without anthracyclines contra-indication (assessed by normal ejection fraction).
* Normal haematological, renal and hepatic functions : PNN \> 2.109 /l, platelets \> 100. 109 /l, Hb \> 10 g/dl, normal bilirubin serum , ASAT and ALAT \< 2,5 ULN, alkaline phosphatases \< 2,5 ULN, creatinin \< 140 µmol/l or creatinin clearance \> 60 ml/min
* Written informed consent dated and signed by the patient

Exclusion Criteria:

* All other breast cancers than those described in inclusion criteria, in particular inflammatory and/or neglected (T4b or T4d) forms.
* Patient presenting with plurifocal tumors, multicentric tumor, bilateral tumor.
* Grade I well differentiated tumor.
* HER2 neu 3 + (ICH or FISH or CISH) tumor.
* Non measurable lesion, in the two diameters, whatever radiological methods used.
* Patient presenting microcalcifications for which breast conservation is not possible.
* Patient already operated for breast cancer or having had primary axillar node dissection.
* Patient having antecedent of other cancer, exception for in situ uterine cervix or basocellular skin cancer, considered as healed.
* Patient presenting another pathology considered as incompatible with patient inclusion in the study
* Patient should not receive treatment with any other investigational drug and should not participate to another clinical study in a delay \< 30 days or should not be pre-treated by cytostatic chemotherapy.
* Antecedents of allergy to polysorbate 80.
* Patient who is pregnant or lactating and not using effective contraceptive method.
* Any psychological, familial, sociological or geographical condition that may potentially hamper compliance with the study protocol and follow up schedule, assessed with the patient prior to registration in the trial

Primary outcomes:
measure: Improvement of complete pathological response rate at surgery after 6 chemotherapy cycles
timeFrame: after 6 cycles of chemotherapy
Secondary outcomes:
measure: Tolerance according to NCI-CTC criteria
timeFrame: after each cycle of chemotherapy
measure: Objective clinical, echographic, mammographic responses after 6 cycles
timeFrame: after every 2 cycles of chemotherapy treatment
measure: Breast conservation rate
timeFrame: at surgery
measure: Study of biological predictive factors of chemosensitivity and resistance by immunological and molecular biology techniques)
timeFrame: before receive chemotherapy
measure: Overall and relapse-free survivals
timeFrame: 5 years after diagnosis
Other outcomes:
Locations:
city: Brive La Gaillarde
country: France
facility: Hospital center
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: Grenoble
country: France
facility: University Hospital La Tronche
city: Lyon
country: France
facility: Edouard Herriot University Hospital
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie de la Loire
Study officials:
affiliation: Centre Jean Perrin
name: Philippe Chollet, Pr
role: STUDY_CHAIR
References:
citation: Roché H, Fumoleau P, Spielman M et al. Breast Cancer Res Treat. 2004;88(suppl1):S16. Abstract 27
citation: Mouret-Reynier MA, Abrial CJ, Ferriere JP, Amat S, Cure HD, Kwiatkowski FG, Feillel VA, Lebouedec G, Penault-Llorca FM, Chollet PJ. Neoadjuvant FEC 100 for operable breast cancer: eight-year experience at Centre Jean Perrin. Clin Breast Cancer. 2004 Oct;5(4):303-7. doi: 10.3816/cbc.2004.n.035.
citation: Wang-Lopez Q, Mouret-Reynier MA, Savoye AM, Abrial C, Kwiatkowski F, Garbar C, DuBray-Longeras P, Eymard JC, Lebouedec G, Vanpraagh I, Penault-Llorca F, Chollet P, Cure H. Is it important to adapt neoadjuvant chemotherapy to the visible clinical response? An open randomized phase II study comparing response-guided and standard treatments in HER2-negative operable breast cancer. Oncologist. 2015 Mar;20(3):243-4. doi: 10.1634/theoncologist.2014-0400. Epub 2015 Jan 30.