Neoadjuvant Chemotherapy Including Sorafenib in Women With Previously Untreated Primary Breast Cancer

Breast Cancer Clinical Trial

— SOFIA  

Official title:

Phase II Study of Neoadjuvant Epirubicin, Cyclophosphamide (EC) + Sorafenib Followed by Paclitaxel (P) + Sorafenib in Women With Previously Untreated

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00548899
• Other study ID #: GBG 45
• Secondary ID: 2007-000124-41
• Status: Completed
• Phase: Phase 2
• First received: October 23, 2007
• Last updated: March 6, 2015
• Start date: November 2007
• Est. completion date: December 2011

Study information

• Verified date: March 2015
• Source: German Breast Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Drug:
• Nexavar (Sorafenib)
Tablet, Sorafenib follows a patient specific escalation scheme starting with 200 mg daily up to a maximum dose of 800 mg daily during EC chemotherapy on day 2-19. The achieved dose will be continued during paclitaxel chemotherapy during week 1-11 all day

Locations

Country	Name	City	State
Germany	St. Gertrauden Krankenhaus	Berlin
Germany	Klinikum der J. W. Goethe Universität	Frankfurt am Main
Germany	Henriettenstiftung	Hannover
Germany	Elisabeth Krankenhaus	Kassel
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Klinikum der Universität zu Köln	Köln
Germany	Klinikum Offenbach	Offenbach
Germany	Klinikum Südstadt	Rostock
Germany	Dr.-Horst-Schmidt-Kliniken GmbH	Wiesbaden

Sponsors (2)

Lead Sponsor	Collaborator
German Breast Group	Bayer

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Loibl S, Rokitta D, Conrad B, Harbeck N, Wüllner 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	to establish the most feasible regimen of EC-P (P-EC) with sorafenib		Time of surgery	No
Secondary	Safety of preoperative regimen		Treatment to Surgery	Yes
Secondary	Determine clinical response rate		Time of surgery	No
Secondary	Histopathological axillary nodal status after neoadjuvant therapy		Time of surgery	No
Secondary	Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response		Baeline till time of surgery	No
Secondary	pCR rate at surgery		Treatment ot Surgery	No

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