Placebo-controlled Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

This is a randomized, double-blind and placebo controlled phase 3 study to evaluate the efficacy and safety of F-627 in women with stage II-IV breast cancer receiving chemotherapy treatment.

This is a randomized, multi-center, single dose, double-blind, placebo controlled phase III study of the efficacy and safety of once-per-cycle of F-627 in women with stage II-IV breast cancer who are receiving myelotoxic TA chemotherapy treatment (Taxotere (docetaxel) + Adriamycin(doxorubicin)). F-627 is designed to treat neutropenia, an abnormally low number of neutrophils (a type of white blood cell) in the blood. Neutropenia is often seen in cancer patients receiving myelotoxic chemotherapy.

The primary objective of this study is to evaluate the efficacy and safety of single fixed dose of F-627 in breast cancer patients experiencing myelotoxic chemotherapy in comparison to placebo. F-627 or placebo is to be administered subcutaneously 24 hours after chemotherapy in each 21-day cycle of chemotherapy treatment (up to 4 cycles). Patients randomized to placebo arm will receive F-627 except in cycle 1. The primary endpoint will be the duration of grade 4 (severe) neutropenia - the number of days in which the patient has had an absolute neutrophil count (ANC \< 0.5 x 10\^9/L) observed in chemotherapy cycle 1.

Eligibility Criteria:
Inclusion Criteria:

1. Show evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.
2. Females ≥ 18 years of age and \< 75 years of age.
3. Diagnosed with Stage II-IV breast cancer.
4. Subject is scheduled to undergo 4 cycles of TA chemotherapy (docetaxel, doxorubicin, 75, and 60 mg/m2, respectively).
5. ECOG Performance status of ≤ 2.
6. White Blood Cell count (WBC) ≥ 4.0 × 109/L, hemoglobin ≥ 11.5 g/dL and a platelet count ≥ 150 × 109/L.
7. 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.
8. 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 is also acceptable forms of contraception as long as they will be used continually throughout the duration of the trial.

Exclusion Criteria:

1. Subject is \<18 or ≥ 75 years of age.
2. Disease progression has occurred while receiving a taxane regimen.
3. Subject has undergone radiation therapy within 4 weeks of enrollment.
4. Subject has undergone bone marrow or stem-cell transplantation.
5. Subject has a history of prior malignancy other than breast cancer that is NOT in remission.
6. Subjects that have used G-CSF or any other drug that may potentiate the release of neutrophils (i.e. lithium) within 6 weeks of the screening period are excluded.
7. Subject has had chemotherapy within 365 days of screening.
8. Subject has documented congestive heart failure, cardiomyopathy or myocardial infarction by clinical diagnosis, ECG test, or any other relevant test.
9. History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
10. Unwillingness to participate in the study.
11. 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.
12. Receiving other investigational drugs or biologics within 1 month or five half lives of enrollment.
13. Any condition, which can cause splenomegaly.
14. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease.
15. ALT, AST, alkaline phosphatase, total bilirubin ≥ 2.5 upper limit of normal.
16. Subject 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.
17. Women who are pregnant or breast-feeding.
18. Subject known to be seropositive for HIV, or who have had an AIDS defining illness or a known immunodeficiency disorder.
19. Subject 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.
20. Subjects with Sickle Cell disease
21. Subjects with known hypersensitivity to E.coli derived proteins' pegfilgrastim' filgrastim, or any other component of the study drug.