Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib in Breast Cancer Patients
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Female, age ≥ 18 years.
- Histologic or cytologic diagnosis of breast carcinoma.
- T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
- Patients with synchronous breast tumors (ipsilateral or bilateral) may be enrolled, provided that none of the tumors is HER2 positive. Protocol-specific biopsy will be performed for each tumor, and each tumor will be assessed separately for pCR rate if the patient is non-metastatic
- Tumor must be HER2 negative by IHC (0 or 1+), or FISH (dual-probe HER2/CEP17 ratio <2.0 with average HER2 copy number <4.0 signals/cell)
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
- ECOG performance 0 or 1.
- Estimated life expectancy of at least 12 weeks.
Adequate organ function including the following:
- Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L
- Hepatic: Bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT or AST ≤ 2.5x ULN, (or ≤5 X with liver metastases)
- Renal: Creatinine ≤ 1.5x ULN
- Left ventricular ejection fraction ≥50%
- Signed informed consent from patient or legal representative.
- Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Exclusion Criteria:
- Prior treatment for locally advanced or metastatic breast cancer.
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Major surgery within 28 days of study drug administration.
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Active bleeding disorder or bleeding site.
- Non-healing wound.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment, with exception of a synchronous HER2 negative breast cancer that is not metastatic
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
- Known history of systemic connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis), vasculitidies (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.
Sites / Locations
- National University Hospital, SingaporeRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Dose-dense doxorubicin/cyclophosphamide
Dose-dense doxorubicin/cyclophosphamide + sunitinib
Doxorubicin 60mg/m2 day 1, every 2 weeks x 4 cycles, Cyclophosphamide 600mg/m2 day1, every 2 weeks x 4 cycles, Subcutaneous pegfilgrastim 6mg, 24-36 hours after doxorubicin/cyclophosphamide
Doxorubicin 60mg/m2 day 1, every 2 weeks x 4 cycles, Cyclophosphamide 600mg/m2 day1, every 2 weeks x 4 cycles, Subcutaneous pegfilgrastim 6mg, 24-36 hours after each cycle of doxorubicin/cyclophosphamide, Oral sunitinib 12.5mg daily for 7 days prior to cycle 1 ddAC (days -7 to 0), Oral sunitinib 12.5mg daily for 5 days prior to cycle 2, 3, 4 ddAC (days 10-14 of preceding cycle)