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

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

The purpose of this study is to determine the efficacy and safety of sorafenib in the neoadjuvant setting in patients with primary breast cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Nexavar (Sorafenib)

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10713
    • St. Gertrauden Krankenhaus
  • Frankfurt am Main, Germany, 60590
    • Klinikum der J. W. Goethe Universität
  • Hannover, Germany, 30559
    • Henriettenstiftung
  • Kassel, Germany, 34177
    • Elisabeth Krankenhaus
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein Campus Kiel
  • Köln, Germany, 50924
    • Klinikum der Universität zu Köln
  • Offenbach, Germany, 63069
    • Klinikum Offenbach
  • Rostock, Germany, 18059
    • Klinikum Südstadt
  • Wiesbaden, Germany, 65199
    • Dr.-Horst-Schmidt-Kliniken GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sorafenib; Single Arm: All patients receive sorafenib in addition to the established chemotherapy	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
to establish the most feasible regimen of EC-P (P-EC) with sorafenib	Time of surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of preoperative regimen	Treatment to Surgery
Determine clinical response rate	Time of surgery
Histopathological axillary nodal status after neoadjuvant therapy	Time of surgery
Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response	Baeline till time of surgery
pCR rate at surgery	Treatment ot Surgery

Collaborators and Investigators

• Sponsor: German Breast Group
• Collaborators: Bayer
• Investigators: Study Chair: Sibylle Loibl, MD, GBG Forschungs GmbH

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 23, 2007
• First Submitted That Met QC Criteria: October 23, 2007
• First Posted (Estimate): October 24, 2007

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: March 6, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Targeted therapy; Neoadjuvant chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: GBG 45; 2007-000124-41 (EudraCT Number)