Clinical trial NCT00751868: FEC With G-CSF Support Followed by Ixabepilone With G-CSF Support as Neoadjuvant Chemotherapy in BC
Official title: NEO-ADIXERN (NEO-ADjuvant IXabepilone in Breast Cancer). A Feasibility Study of Dose-dense FEC With G-CSF Support Followed by Dose-dense Ixabepilone With G-CSF Support as Neoadjuvant Chemotherapy in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Consorzio Oncotech
Sponsor class: OTHER
First posted: 2008-09-12
Enrollment: 47
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the feasibility of Ixabepilone (4 cycles) administered every 14 days with the support of G-CSF sequentially to the combination of Fluorouracil, Epirubicin and Cyclophosphamide (4 cycles) administered every 14 days with the support of G-CSF.

To evaluate the efficacy (in terms of pathologic Complete Responses in the breast and in the axilla), the dose reduction rate, the median treatment delay and the discontinuation rate due to toxicity of the regimen.

Detailed description: Estrogen receptor negative breast cancer may be defined as distinct biologic subtype disease, more aggressive with a typical molecular portrait. \[30\] This subtype seems to have a poor prognosis and poor treatment options because these patients are not candidate to hormonal therapy. Novel treatment strategies focusing upon this subtype are necessary in the future. \[31\] There are reports of clinical benefit in estrogen receptor negative patients treated with dose-dense chemotherapy (see background CALGB 9741 and MIG-1 study). In the CALGB 9741 study, patients randomized to receive dose-dense regimens experienced severe toxicities during paclitaxel treatment leading to dose reduction in 7% and 5%respectively.

Ixabepilone has shown consistent activity and an acceptable safety profile in patients with all stages breast cancer. This phase II study evaluate the feasibility of dose-dense Ixabepilone (4 cycles) given sequentially to the combination of Fluorouracil, Epirubicin and Cyclophosphamide (4 cycles) all given every 14 days with the support of Filgrastim as neo-adjuvant treatment for ER-negative breast cancer patients.

Eligibility criteria: Inclusion Criteria:

* Histological documented diagnosis of breast cancer by incisional biopsy
* Clinical T\>=2
* Females age \>= 18 and \<= 70 years
* ECOG performance status 0-1
* No prior treatment for breast cancer excluding therapy for DCIS
* Subjects with hormone replacement therapy are eligible if this therapy is discontinued at least 2 weeks before starting therapy
* Neutrophils \> 2x109/L, Hgb \> 9 g/dL, platelets \> 100x109/L
* Total bilirubin \< 1 time the upper limit of normal (ULN) of the Institutional normal values and AST and/or ALT \< 2.5 ULN, alkaline phosphatase \< 2.5 ULN
* Serum creatinine \< 1.5 times the upper limit of normal (ULN)
* Normal cardiac function (normal ECG required in all patients, normal ECG and MUGA or Echocardiography with EF only in HER-2 positive patients)
* Negative pregnancy test prior to inclusion in the study (if potentially childbearing)
* Signed Informed consent

Exclusion Criteria:

* Prior or current history of ipsilateral or controlateral breast invasive cancer. A past or current history of ipsilateral ductal carcinoma in situ or ipsilateral/controlateral lobular neoplasia in situ are not an exclusion criteria as well as a controlateral ductal carcinoma in situ removed by mastectomy
* Inflammatory breast cancer
* Metastatic breast cancer (M1)
* Histology other than adenocarcinoma of the breast
* Male patients
* Pregnant or lactating women or women of childbearing potential (e.g. not using adequate contraception)
* Patients unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational drug
* History of prior or concomitant malignancies other than curatively treated basal cell skin cancer or excised cervical carcinoma in situ
* Symptomatic peripheral neuropathy \> grade 1 according to the NCI CTC
* Other serious illness or medical condition:
* Congestive hearth failure or angina pectoris even if it is medically controlled. In particular, Ejection Fraction (EF) below the Institutional normal value for MUGA Fraction (EF) below the Institutional normal value for MUGA, or below 50% for ECHO
* Previous history of myocardial infarction uncontrolled, high-risk ipertension or arrhythmia
* History of significant neurological or psychiatric disorders including dementia or seizures
* Active infection, active peptic ulcer, unstable diabetes mellitus or contraindications for the use of steroids
* History of previous or concomitant malignancies other than curatively treated basal cell skin cancer or excised cervical carcinoma in situ
* Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational regimen within 30 days prior to study entry
* Prior severe HSR to agents containing Cremophor EL

Primary outcomes:
measure: Pathologic Complete Response (pCR)
timeFrame: one year
Secondary outcomes:
measure: Feasibility/Tolerability for an individual patient is defined as the absence of hematologic toxicities requiring dose reduction as per protocol
timeFrame: one year
Other outcomes:
Locations:
city: Treviglio
country: Italy
facility: Azienza Osped.Treviglio - Caravaggio
state: BG
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo
state: BN
city: Campabasso
country: Italy
facility: Ospedale Civile di Campobasso - A. Cardarelli
state: CB
city: Lanciano
country: Italy
facility: Ospedale civile Renzetti di Lanciano
state: CH
city: Como
country: Italy
facility: Azienda Ospedaliera S. Anna
state: CO
city: Catania
country: Italy
facility: Azienda Ospedaliera Nesina Garibaldi
state: CT
city: Genova
country: Italy
facility: I.S.T. - Istituto Nazionale per la Ricerca sul Cancro
state: GE
city: Mecerata
country: Italy
facility: Presidio Ospedaliero di Macerata
state: MC
city: Sesto San Giovanni
country: Italy
facility: I.R.C.C.S. Multimedica - Casa di Cura Accreditata
state: Milano
city: Perugia
country: Italy
facility: Azienda Ospedaliera R. Silvestrini
state: PG
city: Sassari
country: Italy
facility: Azienda Ospedaliera SS. Annunziata
state: SS
city: Negrar
country: Italy
facility: Ospedale S. Cuore Don Calabria
state: Verona
city: Napoli
country: Italy
facility: Ist. Nazionale per lo Studio e la Cura dei Tumori - Fondazione Pascale
city: Napoli
country: Italy
facility: Università Federico II
city: Roma
country: Italy
facility: Istituto Regina Elena
Study officials:
affiliation: Ospedale Sacro Cuore - Dipartimento di Oncologia Medica
name: Marco MV Venturini, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clavarezza M, Bordonaro R, Daniele B, Ferrandina G, Barni S, Turazza M, Coati F, De Matteis A, De Placido S, Cognetti F, Olmeo NA, Carrozza F, Bruzzi P, Del Mastro L; Gruppo Italiano Mammella. Dose-dense FEC followed by dose-dense ixabepilone as neoadjuvant treatment for breast cancer patients: a feasibility study. Oncologist. 2013;18(8):924-5. doi: 10.1634/theoncologist.2013-0222. Epub 2013 Aug 12.