Dose-Finding Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

• Duration of Grade 3 and Grade 4 Neutropenia for each of 4 Chemotherapy cycles. [ Time Frame: Measured for each of the 4, 21 day chemotherapy cycles. ] [ Designated as safety issue: No ]
  The duration of Grade 3 & Grade 4 neutropenia will be measured for each patient during each chemotherapy cycle administered (up to 4 cycles, each cycle is expected to last 21 days). The duration of Grade 3 & 4 neutropenia is expected to be between days 4-10 (on average) during each chemotherapy cycle. Grade 3 neutropenia is when a patient's ANC < 1.0 × 10^9/L, Grade 4 neutropenia is when a patient's ANC < .5 × 10^9/L
• The incidence rate of febrile neutropenia [ Time Frame: Measured for each of the 4, 21 day chemotherapy cycles. ] [ Designated as safety issue: Yes ]
  The incidence rate of febrile neutropenia for each arm of the study will be recorded for 4 chemotherapy cycles. Each cycle is expected to last 21 Days.
• The duration of total grade 2 neutropenia [ Time Frame: Measured for each of the 4, 21 day chemotherapy cycles. ] [ Designated as safety issue: No ]
  After randomization, the duration of time for which grade 2 neutropenia (ANC < 1.5 × 109/L) occurs for each 21 day chemotherapy cycle will be recorded.
• The time to ANC recovery post nadir [ Time Frame: Measured for each of the 4, 21 day chemotherapy cycles. ] [ Designated as safety issue: No ]
  The time to ANC recovery post nadir for each patient, for each of their chemotherapy cycles will be recorded; recovery for this protocol is defined as achieving an ANC ≥ 2.0 × 10^9/L after the expected ANC nadir (expected nadir is typically 4-6 days post chemotherapy administration). Each chemotherapy cycle is expected to last 21 days.

This is a randomized open label dose finding study to evaluate the efficacy and safety of F-627 on women with Stage II-III breast cancer receiving chemotherapy treatment.

This is a randomized, multi-center, dose finding, open label, positive controlled Phase II study of the efficacy and safety of once-per-cycle of F-627 compared with Neulasta® (pegfilgrastim) in women with breast cancer who are receiving myelotoxic TC chemotherapy (Taxotere (docetaxel) + cyclophosphamide).

The primary objective of this study is to evaluate the efficacy and safety of various single cycle doses of F-627 as compared with the standard dosing of Neulasta® (pegfilgrastim) in breast cancer patients experiencing myelotoxic chemotherapy. Myelotoxicity in this study will be defined by the duration of moderate neutropenia; the number of days in which the patient has had an absolute neutrophil count (ANC) < 1.0 × 10^9/L during the first cycle of their chemotherapy treatment (each chemotherapy cycle is expected to last 21 days). This, by definition, includes grade 3 (moderate) and grade 4 (severe) neutropenia. Doses of F-627 to be tested are 80 µg/kg/dose, 240 µg/kg/dose, and 320 µg/kg/dose.

• Drug: F-627
  subcutaneous injection given 1 per chemotherapy.
• Drug: Neulasta® (pegfilgrastim)
  Single dose injection given once per chemotherapy cycle.

• Experimental: 80 µg/kg/dose of F-627
  Intervention: Drug: F-627
• Experimental: 240 µg/kg/dose of F-627
  Intervention: Drug: F-627
• Experimental: 320 µg/kg/dose of F-627
  Intervention: Drug: F-627
• Active Comparator: Neulasta® (pegfilgrastim)
  Intervention: Drug: Neulasta® (pegfilgrastim)

Inclusion Criteria:

• Show evidence of a signed (personally or by a legally acceptable representative) and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.
• Females ≥ 18 years of age.
• Diagnosed with Stage II-III breast cancer.
• Subject is scheduled to undergo 4 cycles of TC chemotherapy (Taxotere and cyclophosphamide, 75 and 600 mg/m2, respectively).
• ECOG Performance status of ≤ 2.
• White Blood Cell count (WBC) ≥ 4.0 × 109/L, hemoglobin ≥ 11.5 g/dL and a platelet count ≥ 150 × 109/L.
• Demonstrate adequate renal, hepatic function (Liver function tests (ALT, AST, alkaline phosphatase and total bilirubin)) should be less than 2.5x upper limits of normal (ULN). Serum creatinine should be less than 1.7x ULN.
• All subjects must agree to use at least one of the following types of contraception: intrauterine device, implantable progesterone device, progesterone intramuscular injection, or oral contraceptive, which has been started at least one month prior to visit one and will continue for the duration of the trial. The contraceptive patch or condom use with spermicide are also acceptable forms of contraception as long as they will be used continually throughout the duration of the trial.

Exclusion Criteria:

• Subject is <18 or ≥ 75 years of age.
• Disease progression has occurred while receiving a taxane regimen.
• Subject has undergone radiation therapy within 4 weeks of enrollment.
• Subject has undergone bone marrow or stem-cell transplantation.
• Subject has a history of prior malignancy other than breast cancer.
• Subjects that have used G-CSF within 6 weeks of the screening period are also excluded
• Subject has had chemotherapy within 365 days of screening
• Subject has documented congestive heart failure, cardiomyopathy or myocardial infarction by clinical diagnosis, ECG test, or any other relevant test.
• History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
• Unwillingness to participate in the study.
• Any underlying medical condition that, in the Investigator's opinion, would make the administration of study drug hazardous to the patient or that would obscure the interpretation of adverse events.
• Receiving other investigational drugs or biologics within 1 month or five half lives of enrollment.
• Any condition, which can cause splenomegaly.
• Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease.
• ALT, AST, alkaline phosphatase > 2.5 upper limit of normal.
• Patients with active infection, or known to be infected with chronic active Hepatitis B within the last 1 year (unless shown at the time of study entry to be Hepatitis B antigen negative), or having any history of Hepatitis C.
• Women who are pregnant or breast-feeding.
• Patients known to be seropositive for HIV, or who have had an AIDS defining illness or a known immunodeficiency disorder.
• Patients with a history of tuberculosis or exposure to tuberculosis. Patients that have received a prior chest X-ray for suspicion of tuberculosis are also excluded unless they have been confirmed to be PPD negative or they had latent tuberculosis that has been previously treated.
• Subjects with Sickle Cell disease
• Subjects with known hypersensitivity to E.coli derived proteins' pegfilgrastim' filgrastim, or any other component of the study drug.