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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT00548899
First received: October 23, 2007
Last updated: May 2, 2012
Last verified: September 2010
  Purpose

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


Condition Intervention Phase
Breast Cancer
Drug: Nexavar (Sorafenib)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Epirubicin, Cyclophosphamide (EC) + Sorafenib Followed by Paclitaxel (P) + Sorafenib in Women With Previously Untreated

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • to establish the most feasible regimen of EC-P (P-EC) with sorafenib [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of preoperative regimen [ Time Frame: Treatment to Surgery ] [ Designated as safety issue: Yes ]
  • Determine clinical response rate [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]
  • Histopathological axillary nodal status after neoadjuvant therapy [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]
  • Correlate baseline and change in tumor and serum genetic, gene expression and proteomic patterns with clinical and pathological response [ Time Frame: Baeline till time of surgery ] [ Designated as safety issue: No ]
  • pCR rate at surgery [ Time Frame: Treatment ot Surgery ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: November 2007
Study Completion Date: December 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548899

Locations
Germany
St. Gertrauden Krankenhaus
Berlin, Germany, 10713
Klinikum der J. W. Goethe Universität
Frankfurt am Main, Germany, 60590
Henriettenstiftung
Hannover, Germany, 30559
Elisabeth Krankenhaus
Kassel, Germany, 34177
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, Germany, 24105
Klinikum der Universität zu Köln
Köln, Germany, 50924
Klinikum Offenbach
Offenbach, Germany, 63069
Klinikum Südstadt
Rostock, Germany, 18059
Dr.-Horst-Schmidt-Kliniken GmbH
Wiesbaden, Germany, 65199
Sponsors and Collaborators
German Breast Group
Bayer
Investigators
Study Chair: Sibylle Loibl, MD GBG Forschungs GmbH
  More Information

Additional Information:
No publications provided

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT00548899     History of Changes
Other Study ID Numbers: GBG 45, 2007-000124-41
Study First Received: October 23, 2007
Last Updated: May 2, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Breast Group:
Neoadjuvant chemotherapy
Targeted therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014