Clinical trial NCT00548899: Neoadjuvant Chemotherapy Including Sorafenib in Women With Previously Untreated Primary Breast Cancer
Official title: Phase II Study of Neoadjuvant Epirubicin, Cyclophosphamide (EC) + Sorafenib Followed by Paclitaxel (P) + Sorafenib in Women With Previously Untreated
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Neoadjuvant chemotherapy
Targeted therapy
Lead sponsor: GBG Forschungs GmbH
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-10-24
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
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 determine the efficacy and safety of sorafenib in the neoadjuvant setting in patients with primary breast cancer

Detailed description: Epirubicin/Cyclophosphamide followed by Paclitaxel (EC/P) is a well tolerated regimen with high clinical activity. Histopathological complete remission after preoperative chemotherapy has a direct correlation with the disease-free and overall survival. The aim of combining a chemotherapy regime with sorafenib in the neoadjuvant setting is to increase the locoregional and systemic outcome of these patients

Eligibility criteria: Inclusion Criteria:

* Unilateral or bilateral primary carcinoma of the breast,
* Tumor lesion in the breast with a palpable size of \>= 2 cm. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion;
* Patients should have stages of disease in which adjuvant chemotherapy would be considered.
* Women of childbearing potential must have a negative serum pregnancy test
* Negative HER-2/neu status
* Karnofsky Performance status index \>= 80%;
* Normal cardiac function
* Laboratory requirements:

Absolute neutrophile count (ANC) \>= 2,0 x 109/L and Platelets \>= 100 x 109/L and Hemoglobin \>= 10 g/dL (\>= 6.2 mmol/L) INR ≤ 1.5 ULN and PTT ≤ 1.5 ULN within 14 days prior to enrolment ASAT or ALAT \< 2.5 x ULN Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and/or ALAT \> 1,5 x UNL associated with alkaline phosphatase \> 2,5 x UNL are not eligible for the study Total bilirubin \< 1 X UNL Creatinine ≤ 175 µmol/L (2 mg/dl). The calculated creatinine clearance should be ≥ 60 mL/min.

Paraffin tumor tissue block and each one serum and one plasma sample centrally made available

* Complete staging work-up within 3 months prior to registration.
* Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.

Exclusion Criteria:

* Patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criteria No. 5.
* Evidence of distant metastasis;
* Prior chemotherapy for any malignancy;
* Prior radiation therapy for breast cancer;
* Preexisting rhagades at hand and feet and other skin problems (e.g. psoriasis)
* Pregnant or lactating patients.
* Pre-existing motor or sensory neuropathy of a severity \>= grade 2 by NCI criteria; 7. Concurrent treatment with: Chronic corticosteroids unless initiated \> 6 months prior to study entry and at low dose (\< 20 mg methylprednisolone or equivalent); Sex hormones. Prior treatment must be stopped before study entry; Patients with increased risk of bleeding due to concurrent therapeutic or prophylactic anticoagulative treatment. Low dose of coumarines are permitted.

Other experimental drugs or any other anti-cancer therapy; Drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days or their expected need 8. Other serious illness or medical condition:

* Previous malignant disease without being disease-free of less than 5 years (except CIS of the Cervix and non-melanomatous skin cancer)
* Known or suspected congestive heart failure (≥NYHA II) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease
* Thrombotic or embolic events
* Hemorrhage/bleeding event ≥ Grade 3 within 4 weeks prior study entry
* Evidence or history of bleeding diathesis or coagulopathy
* History of significant neurological or psychiatric disorders
* Patients with seizure disorders requiring medication such as steroids or antiepileptics
* Currently active infection
* History of HIV infection or chronic hepatitis B or C
* Serious non healing wound, ulcer or bone fracture
* Patients with prior immunosuppressive treatment
* Severe pulmonary condition/illness
* Disease significantly affecting gastrointestinal function,
* Patients with severe liver disease
* Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
* Definite contraindications for the use of corticosteroids
* Inadequate general condition (not fit for anthracycline/taxane-containing chemotherapy)

Primary outcomes:
measure: to establish the most feasible regimen of EC-P (P-EC) with sorafenib
timeFrame: Time of surgery
Secondary outcomes:
measure: Safety of preoperative regimen
timeFrame: Treatment to Surgery
measure: Determine clinical response rate
timeFrame: Time of surgery
measure: Histopathological axillary nodal status after neoadjuvant therapy
timeFrame: Time of surgery
measure: Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response
timeFrame: Baeline till time of surgery
measure: pCR rate at surgery
timeFrame: Treatment ot Surgery
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: St. Gertrauden Krankenhaus
city: Frankfurt am Main
country: Germany
facility: Klinikum der J. W. Goethe Universität
city: Hannover
country: Germany
facility: Henriettenstiftung
city: Kassel
country: Germany
facility: Elisabeth Krankenhaus
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln
city: Offenbach
country: Germany
facility: Klinikum Offenbach
city: Rostock
country: Germany
facility: Klinikum Südstadt
city: Wiesbaden
country: Germany
facility: Dr.-Horst-Schmidt-Kliniken GmbH
Study officials:
affiliation: GBG Forschungs GmbH
name: Sibylle Loibl, MD
role: STUDY_CHAIR
References:
citation: Loibl S, Rokitta D, Conrad B, Harbeck N, Wullner M, Warm M, Schwedler K, Gerber B, Schrader I, Eidtmann H, Mehta K, Fuhr U, von Minckwitz G. Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA. Breast Care (Basel). 2014 Jul;9(3):169-74. doi: 10.1159/000363430.