Breast Cancer
Conditions
Keywords
Breast Cancer, Early Stage, High Risk, Node Positive, Doxorubicin, Cyclophosphamide, Paclitaxel, Sorafenib
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.
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.
Interventions
DRUGDoxorubicin
DRUGCyclophosphamide
DRUGPaclitaxel
DRUGSorafenib
Sponsors
Bayer
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib Doxorubicin 60mg/m2 IV, Cyclophosphamide 600mg/m2 IV every 3 weeks for a total of 12 weeks followed by 12 weeks of paclitaxel (either 175mg/m2 IV every three weeks or 80mg/m2 IV weekly) and sorafenib 400mg twice daily by mouth (up to a maximum of 1 year). | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 21 |
| Overall Study | Physician Decision | 8 |
Baseline characteristics
| Characteristic | Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib |
|---|---|
| Age Continuous | 54 years |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 7 / 45 |
Outcome results
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.
Time frame: 18 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib | 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. | 40 percentage of patients |