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

Breast Cancer Clinical Trial

Official title:

A Single-Center, Open-Label, Dose-Escalation Phase I Clinical Trial of Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein for Injection as an Adjuvant to Chemotherapy in Subjects With Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527746
• Other study ID #: 2012-F-627-CH1
• Status: Completed
• Phase: Phase 1
• Start date: December 2012
• Est. completion date: December 2013

Study information

• Verified date: July 2023
• Source: EVIVE Biotechnology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18-75 years old.

2. Female postoperative breast cancer patients who require adjuvant chemotherapy, and are planned to receive 4 cycles of EC chemotherapy;

3. East Cooperative Oncology Group (ECOG) performance 0-1.

4. Absolute neutrophil count (ANC) = 2.0 × 10^9/L, hemoglobin (Hb) = 11.0 g/dl, and platelets (PLT) = 100 × 10^9/L prior to chemotherapy.

5. Hepatic and renal function within the normal range;.

6. Left ventricular ejection fraction (LVEF) > 50%.

7. Willing to sign the informed consent form and able to comply with protocol requirements

Exclusion Criteria:

1. Women in pregnancy or breastfeeding; Women of child-bearing potential have a positive pregnancy test result prior to the first dose;

2. Life expectancy less than 12 months;

3. Radiation therapy within 4 weeks prior to enrollment;

4. Breast cancer patients who have received neoadjuvant chemotherapy before radical mastectomy;

5. Prior bone marrow or stem cell transplant;

6. With other malignant tumors other than breast cancer;

7. Have received granulocyte colony stimulating factor (G-CSF) treatment within 6 weeks prior to enrollment;

8. Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, electrocardiograph (ECG) or other approaches;

9. With any disease that may cause splenomegaly;

10. With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C;

11. History of tuberculosis (TB); history of TB exposure, unless negative for tuberculin test; TB patients undergoing treatment; or suspected TB evaluated by chest x-ray;

12. Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS);

13. With sickle cell anemia;

14. With alcohol or drug abuse that may affect the compliance with the study;

15. With known hypersensitivity to E. coli derived proteins, G-CSF, or excipients;

16. Has received any other investigational drug within 4 weeks prior to enrollment;

17. Patients with diseases or symptoms unsuitable for participating in the clinical trial based on the investigator's judgment;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neutropenia

Intervention

Drug:
• F-627
F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
• EC regimen
Epirubicin 100 mg/m^2 (in vein) and Cyclophosphamide 600 mg/m^2 (in vein) on Day 1 of each cycle for 4 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
EVIVE Biotechnology	Fudan University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 4 cycles (about 84 days)
Primary	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).	Up to 21 days
Secondary	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).	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Cycle 1 and cycle 3 (each cycle was about 21 days)
Secondary	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.	Up to 4 cycles (84 days)
Secondary	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.	Up to 4 cycles (84 days)
Secondary	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.	Up to 4 cycles (84 days)
Secondary	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.	Up to 4 cycles (84 days)
Secondary	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.	Up to 4 cycles (84 days)
Secondary	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.	Up to 4 cycles (84 days)