Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor

• Status: Unknown status
• Trial end date: 2017-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is a single-centre, phase II randomized study of doxorubicin and cyclophosphamide (AC) with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy.

A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration.

A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study. Eligible patients will be randomized 1:1 to either arm A or arm B. Patients will be stratified according to metastatic status (metastatic vs non-metastatic) and presence or absence of clinical T4 disease.

Arm A (Control arm):

Doxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles

Arm B (Experimental arm):

Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily (duration and dose as determined from the lead-in phase I study) Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)

DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject:

Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1, and on days 1 and 15 of each subsequent cycle. In addition, patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Treatments: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Sunitinib

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 must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.

• Karnofsky performance status of 70 or higher.

• 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.

• 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), vasculitides (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.

• Known history of renal impairment, defined as a Glomerular Filtration Rate (GFR) of less than 30ml/minute.