Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00544167
Recruitment Status : Completed
First Posted : October 16, 2007
Results First Posted : January 25, 2013
Last Update Posted : April 1, 2013
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
Sorafenib is being looked at in a number of solid tumor settings including breast cancer. This trial is designed as a pilot study to assess the safety and tolerability of a novel oral agent in combination with standard chemotherapy in the treatment of early stage node positive or otherwise high-risk breast cancer. If this should prove to be a tolerable regimen for patients, this would provide rationale for further studies in a larger randomized fashion.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Sorafenib Not Applicable

Detailed Description:

Primary Objectives The primary objective is to assess the safety and tolerability of doxorubicin / cyclophosphamide followed by paclitaxel in combination with sorafenib in patients with early stage node positive or otherwise high-risk breast cancer.

Secondary Objectives The secondary objectives are to assess activity in the form of recurrence-free-interval, distant recurrence-free interval,and overall survival in this pilot study of doxorubicin / cyclophosphamide followed by paclitaxel in combination with sorafenib in patients with early stage node positive or otherwise high-risk breast cancer.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Adjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel Plus Sorafenib in Women With Node Positive or High-Risk Early Stage Breast Cancer
Study Start Date : May 2007
Actual Primary Completion Date : January 2008
Actual Study Completion Date : April 2011

Arm Intervention/treatment
Experimental: Intervention
All patients received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) both administered intravenously day 1 every 3 weeks for four cycles, followed by paclitaxel 175 mg/m2 intravenously day 1 every 3 weeks for four cycles or 80 mg/m2 for twelve weeks (physician discretion), combined with sorafenib 400 mg orally twice daily. Sorafenib was held during radiation therapy where indicated and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy where indicated.
Drug: Doxorubicin
Other Name: Adriamycin

Drug: Cyclophosphamide
Other Name: Cytoxan

Drug: Paclitaxel
Other Name: Taxol

Drug: Sorafenib
Other Name: Nexavar

Primary Outcome Measures :
  1. The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0. [ Time Frame: 18 Months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically-confirmed breast cancer with an interval between definitive surgery that includes axillary lymph node involvement assessment and initiation of study treatment of less than or equal to 84 days.
  • Definitive surgery - either mastectomy with axillary node involvement assessment, or breast conserving surgery with axillary node assessment. Margins of resected specimen must be free of invasive disease and/or ductal carcinoma in situ (DCIS).
  • Stage I, II, IIIA, and IIIC (T1-3, N3a only). Patients must be either lymph node positive or high-risk node negative.
  • Age > 18 years.
  • ECOG performance status 0 or 1.
  • Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) by Echocardiography or MUGA scan and electrocardiogram (ECG) within 35 days prior to initiation of study treatment.
  • Patients must have adequate bone marrow function
  • Patients must have normal liver function (
  • Serum creatinine <= 2mg/dl
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored.

Exclusion Criteria:

  • Prior systemic anticancer therapy for breast cancer (immunotherapy, chemotherapy, hormonal therapy).
  • Patients with HER2 positive breast cancer as determined by FISH or IHC3+ standing are ineligible for this trial.
  • Prior anthracycline or taxane therapy.
  • Prior radiation therapy for breast cancer.
  • Bilateral invasive disease.
  • Pre-existing motor or sensory neurotoxicity of a severity ≥ 2 by NCI CTCAE v 3.0 criteria.
  • Cardiac disease that includes: myocardial infarction; angina, congestive heart failure, arrhythmia; valvular heart disease; cardiomegaly on chest imaging or ventricular hypertrophy on ECG - unless the LVEF is within normal range for the institution; patients with poorly controlled hypertension (defined as systolic blood pressure > 150 and /or diastolic blood pressure > 100 mmHg on antihypertensive medications); patients who receive medications for angina, arrhythmias, or congestive heart failure.
  • Current therapy with raloxifene, tamoxifen or other selective estrogen receptor modulator
  • Concurrent treatment with ovarian hormonal replacement therapy.
  • History of prior malignancy within 5 years with the exception of skin cancer or cervical carcinoma in situ.
  • Women who are pregnant (positive pregnancy test) or breast feeding. Subjects of childbearing potential must use effective birth control measures during treatment.
  • Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment.
  • Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • Thrombotic or embolic events such as a stroke and transient ischemic attack within the past 6 months.
  • Pulmonary hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 3 within 4 weeks of first dose of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00544167

United States, Florida
Integrated Community Oncology Network
Jacksonville, Florida, United States, 32256
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Study Chair: Denise Yardley, M.D. SCRI Development Innovations, LLC

Additional Information:
Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00544167     History of Changes
Other Study ID Numbers: SCRI BRE 112
First Posted: October 16, 2007    Key Record Dates
Results First Posted: January 25, 2013
Last Update Posted: April 1, 2013
Last Verified: March 2013

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer
Early Stage
High Risk
Node Positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors