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English Summary - Sofia

Current Status:

Recruiting

Title

Phase II study of neoadjuvant epirubicin, cyclophosphamide (EC) + sorafenib followed by paclitaxel (P) + sorafenib in women with previously untreated primary breast cancer.

Trial design

Open-label, multicenter, single-arm, phase II study.

Treatment

Sorafenib follows a patient specific escalation scheme starting with 200 mg daily up to a maximum dose of 800 mg daily.

Co-medication:

Neoadjuvant chemotherapy consisting of four cycles of 12 weeks of weekly paclitaxel (80 mg/m2, i.v.) followed by EC (epirubicin 90 mg/m2, i.v. on day 1 and cyclophosphamide 600 mg/m2, i.v., on day 1).

 

Rationale

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. Currently, there is little information on safety and toxicity of this combination. current studies assume even better results with the reversed scheme of firstly given P followed by EC.

Patient population

Inclusion criteria: 

1. Written informed consent for all study procedures including an additional core biopsy after the first 4 cycles of EC must be obtained and documented according to the local regulatory requirements
2. Complete baseline documentation sent to GBG Forschungs GmbH
3. 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
4. Patients should have stages of disease in which adjuvant chemotherapy would be considered. In patients with multifocal or multicentric breast cancer, the largest lesion should be measured
5. Age ≥ 18 years
6. Negative HER-2/neu status
7. Paraffin tumor tissue block and each one serum and one plasma sample centrally made available

Exclusion criteria:

1. Patients with low or moderate risk, who are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criteria No. 5
2. Evidence of distant metastasis
3. Prior chemotherapy for any malignancy
4. Prior radiation therapy for breast cancer
5. Preexisting rhagades at hand and feet and other skin problems (e.g. psoriasis)
6. Other serious illness or medical condition:
   
   • 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 (systolic blood pressure >150 mm Hg or > 90 mmHg diastolic blood pressure under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease
   • Thrombotic or embolic events including transient ischemic attacks within the past six months
   • 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 including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
   • 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, e.g. malabsorption syndrome, resection of the stomach or small bowel, ulcerative colitis;
   • Patients with severe liver disease
   • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
7. Definite contraindications for the use of corticosteroids

Primary Objective

Rate of histopathological complete remission at the time of surgery

Secondary Objectives 

1. Safety of preoperative regimen
2. Disease free and overall survival
3. Determine clinical response rate
4. Histopathological axillary nodal status after neoadjuvant therapy
5. Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response

Primary Endpoint

Establishment of the most feasible regimen of EC-P (P-EC) with Sorafenib.

Addenda

Protocol version 6.0 (final) 16.01.2010

Reference

Loibl S et al., Sorafenib (Bay 43-9006) in patients with metastatic breast cancer - a phase II multicentre open study Poster Award: 27. Deutscher Krebskongress (DKG) Berlin, March 2006

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Study Group: German Breast Group GBG

Sponsor: GBG Forschungs GmbH

Study Chair: PD Dr. Sibylle Loibl

Study Co-Chair: Dr. med. Petra Vogel

Clinical Project Management:
Dr. Kirsten Plückhahn

Data Management / Biometry:
Keyur Mehta

Study start: First submission: 01.03.2007

Approval: 28.08.2007 + 27.11.2007 + 29.10.2008 + 04.2010

Enrollment period:
Q III 2007 - Q IV 2010

Proposed accrual: 36

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