Study of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

Study Overview
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Brief Summary
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A Phase I, dose escalation study to evaluation the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients who received up to 4 cycles of Epirubicin and Cyclophosphamide. 18 patients (6 patients each cohort) were assigned to three escalated dose cohorts of 80, 240 and 320 µg/kg.

Detailed Description
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A Phase I, dose escalation study to evaluation the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients receiving 4 cycles of EC chemotherapy (Epirubicin plus Cyclophosphamide). 18 patients (6 patients each cohort) were assigned to three sequential doses cohort of F-627 at the dose of 80, 240 and 320 µg/kg. The patients received chemotherapy (100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide) administrated by i.v. injection on Day 1 and F-627 by s.c. injection on Day 3 of each cycle for 4 cycles. If no dose-limiting toxicity (DLT) was observed in 6 patients during first cycle, the next cohort was escalated. Blood samples were collected for completed blood counts with differential, serum F-627 concentration and safety evaluation at different point following F-672 injection. The decision to proceed to the next higher dose was be made jointly by the sponsor's medical expert and the investigator based upon the review of safety data in the first cycle treatment.

Official Title
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A Phase I, Single Center, Open-label, Dose Escalation Study of Recombinant Human Granulocyte Colony-stimulating Factor Fc Fusion Protein (F-627) in Breast Cancer Patient Receiving Adjuvant Chemotherapy

Conditions
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Neutropenia, Breast Cancer

Intervention / Treatment
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* Biological: F-627
* Drug: EC regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old. Female breast cancer patients after resection who planned to receive 4 cycles of adjuvant chemotherapy contains epirubicin and cyclophosphamide. East Cooperative Oncology Group (ECOG) performance 0-1. Absolute neutrophil count (ANC) ≥ 2.0 × 109/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 109/L prior to chemotherapy. Liver and kidney function tests were within normal reference range. Left ventricular ejection fraction (LVEF) > 50%. Willing to provide written informed consent and to compliant study procedure. Exclusion Criteria: Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment. Expected survival < 12 months. Patients received radiotherapy within 4 weeks prior to enrollment. Patients received neoadjuvant chemotherapy prior to resection of breast cancer. Patients received bone marrow or hemopoietic stem cell transplantation; Patient was with metastatic cancer other than breast cancer. Patients received Granulocyte Colony-stimulating Factor (G-CSF) treatment within 6 weeks prior to enrollment. Acute congestive heart failure, myocardial disease, or myocardial infarction diagnosed by clinical, electrocardiography, or any other medical procedure. Any disease that possibly cause splenomegaly. Acute infections, chronic active hepatitis B infection within 1 year (except subject with negative hepatitis B antigen prior to enrollment) or history of hepatitis C infection. Patients with active tuberculosis (TB), or had ever the history of close contact with patients with TB except negative result in tuberculin test; or under TB treatment; or suspected TB by chest X-ray. Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS). Patients with sickle-cell anemia. Patients with alcohol abuse or drug addiction that may affect the compliance of the study. Patients with allergy to proteins extracted from Escherichia coli, G-CSF, or drug excipient. Patients took other investigational products within 4 weeks prior enrollment. Patients with diseases or symptoms that may not be suitable to be enrolled in this study based on investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F-627 80 µg/kg<br>F-627 at the dose of 80 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles. | Biological: F-627<br>* F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.<br>* Other names: rh G-CSF Fc fusion protein;Drug: EC regimen<br>* Epirubicin 100 mg/m2 (in vein) and Cyclophosphamide 600 mg/m2 (in vein) on Day 1 of each cycle for 4 cycles.<br>* Other names: Epirubicin + Cyclophosphamide;|
| Experimental: F-627 240 µg/kg<br>F-627 at the dose of 240 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles. | Biological: F-627<br>* F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.<br>* Other names: rh G-CSF Fc fusion protein;Drug: EC regimen<br>* Epirubicin 100 mg/m2 (in vein) and Cyclophosphamide 600 mg/m2 (in vein) on Day 1 of each cycle for 4 cycles.<br>* Other names: Epirubicin + Cyclophosphamide;|
| Experimental: F-627 320 µg/kg<br>F-627 at the dose of 320 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles. | Biological: F-627<br>* F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.<br>* Other names: rh G-CSF Fc fusion protein;Drug: EC regimen<br>* Epirubicin 100 mg/m2 (in vein) and Cyclophosphamide 600 mg/m2 (in vein) on Day 1 of each cycle for 4 cycles.<br>* Other names: Epirubicin + Cyclophosphamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as measure of safety and tolerability of F-627 in female patients wiht breast cancer receiving adjuvant chemotherapy. |  | Up to 4 cycles (about 84 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration as a measure of pharmacokinetics profile of F-627. |  | Cycle 1 and cycle 3 (each cycle was about 21 days) | 
| Area Under the Curve as a measure of pharmacokinetics profile of F-627. |  | Cycle 1 and cycle 3 (each cycle was about 21 days) | 
| Clearance and Mean Residence Time as a measure of pharmacokinetics profile of F-627. |  | Cycle 1 and cycle 3 (each cycle was about 21 days) | 
| Absolute Neutrophil Count changes over time as measure of pharmacodynamics of F-627. |  | Up to 4 cycles (84 days) |