Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544167
• Other study ID #: SCRI BRE 112
• Status: Completed
• Phase: N/A
• First received: October 15, 2007
• Last updated: March 25, 2013
• Start date: May 2007
• Est. completion date: April 2011

Study information

• Verified date: March 2013
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: April 2011
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Doxorubicin

• Cyclophosphamide

• Paclitaxel

• Sorafenib

Locations

Country	Name	City	State
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Methodist Cancer Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Bayer

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		18 Months	Yes

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