Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer

• ClinicalTrials.gov Identifier: NCT00544167
• Recruitment Status: Completed
• First Posted: October 16, 2007
• Results First Posted: January 25, 2013
• Last Update Posted: April 1, 2013
• Sponsor: SCRI Development Innovations, LLC
• Collaborator: Bayer
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

Study Description

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: N/A
• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

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

Bayer

Investigators

• Study Chair: Denise Yardley, M.D.; SCRI Development Innovations, LLC

More Information

Additional Information:

Related Info 

Publications:

Spigel DR, Hainsworth JD, Burris HA 3rd, Molthrop DC, Peacock N, Kommor M, Vazquez ER, Greco FA, Yardley DA. A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer. Clin Adv Hematol Oncol. 2011 Apr;9(4):280-6.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00544167
• Other Study ID Numbers: SCRI BRE 112
• First Posted: October 16, 2007
• 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; Doxorubicin; Cyclophosphamide; Paclitaxel; Sorafenib

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Cyclophosphamide; Doxorubicin; Sorafenib; 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