A Phase I, dose escalation study to evaluate 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.
A Phase I, dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients receiving 4 cycles of EC (Epirubicin plus Cyclophosphamide) chemotherapy. 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/m\^2 epirubicin and 600 mg/m\^2 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 made jointly by the sponsor's medical expert and the investigator based upon the review of safety data in the first cycle treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
Epirubicin 100 mg/m\^2 (in vein) and Cyclophosphamide 600 mg/m\^2 (in vein) on Day 1 of each cycle for 4 cycles.
Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
Safety endpoints include incidence rate and severity of adverse events (AEs), laboratory measurements, physical examinations, vital signs, and performance status. Severity of AEs were assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.03 criteria.
Time frame: Up to 4 cycles (about 84 days)
Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
Tolerability should be assessed by dose-limiting toxicity (DLT). DLT is defined as any grade 3 or greater adverse event related to the investigational drug that observed in cycle 1 (21 days).
Time frame: Up to 21 days
T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using enzyme linked immunosorbent assay (ELISA).
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
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Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)