Breast Cancer Treated by Neoadjuvant Chemotherapy

Sponsor

Centre Jean Perrin (Other)

Overall Status

Completed

CT.gov ID

NCT00425516

Collaborator

(none)

264

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Individualized Chemotherapy	Drug: Taxotere Drug: 5-Fluorouracil Drug: Epirubicin Drug: Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2007

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: standard (A) 3 FEC100 followed 3 Taxotere
Experimental: Modulated (B) possibility treatments receive: 2 FEC100 followed by 4 Taxotere 4 FEC100 followed by 2 Taxotere 6 FEC 100	Drug: Taxotere Other Names: Docetaxel Drug: 5-Fluorouracil Drug: Epirubicin Drug: Cyclophosphamide

Arm

Intervention/Treatment

No Intervention: standard (A)

3 FEC100 followed 3 Taxotere

Experimental: Modulated (B)

possibility treatments receive: 2 FEC100 followed by 4 Taxotere 4 FEC100 followed by 2 Taxotere 6 FEC 100

Drug: Taxotere

Other Names:

Docetaxel

Drug: 5-Fluorouracil

Drug: Epirubicin

Drug: Cyclophosphamide

Outcome Measures

Primary Outcome Measures

Improvement of complete pathological response rate at surgery after 6 chemotherapy cycles [after 6 cycles of chemotherapy]

Secondary Outcome Measures

Tolerance according to NCI-CTC criteria [after each cycle of chemotherapy]
Objective clinical, echographic, mammographic responses after 6 cycles [after every 2 cycles of chemotherapy treatment]
Breast conservation rate [at surgery]
Study of biological predictive factors of chemosensitivity and resistance by immunological and molecular biology techniques) [before receive chemotherapy]
Overall and relapse-free survivals [5 years after diagnosis]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital center	Brive La Gaillarde	France	19100
2	Centre Jean Perrin	Clermont Ferrand	France	63011
3	University Hospital La Tronche	Grenoble	France	38043
4	Edouard Herriot University Hospital	Lyon	France	69000
5	Institut Jean Godinot	Reims	France	51056
6	Institut de Cancérologie de la Loire	Saint Priest en Jarez	France	42270