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Completed

NCT Number: NCT02527746

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

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.

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Key information

Conditions

Neutropenia Agranulocytosis Breast Cancer Breast Diseases Breast Neoplasms Cytopenia Hematologic Diseases Hemic and Lymphatic Diseases Leukocyte Disorders Leukopenia Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18-75 years old.
  • Female postoperative breast cancer patients who require adjuvant chemotherapy, and are planned to receive 4 cycles of EC chemotherapy;
  • East Cooperative Oncology Group (ECOG) performance 0-1.
  • 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.
  • Hepatic and renal function within the normal range;.
  • Left ventricular ejection fraction (LVEF) > 50%.
  • Willing to sign the informed consent form and able to comply with protocol requirements

Exclusion criteria

  • Women in pregnancy or breastfeeding; Women of child-bearing potential have a positive pregnancy test result prior to the first dose;
  • Life expectancy less than 12 months;
  • Radiation therapy within 4 weeks prior to enrollment;
  • Breast cancer patients who have received neoadjuvant chemotherapy before radical mastectomy;
  • Prior bone marrow or stem cell transplant;
  • With other malignant tumors other than breast cancer;
  • Have received granulocyte colony stimulating factor (G-CSF) treatment within 6 weeks prior to enrollment;
  • Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, electrocardiograph (ECG) or other approaches;
  • With any disease that may cause splenomegaly;
  • With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C;
  • 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;
  • Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS);
  • With sickle cell anemia;
  • With alcohol or drug abuse that may affect the compliance with the study;
  • With known hypersensitivity to E. coli derived proteins, G-CSF, or excipients;
  • Has received any other investigational drug within 4 weeks prior to enrollment;
  • Patients with diseases or symptoms unsuitable for participating in the clinical trial based on the investigator's judgment;

Treatment and study plan

F-627

Drug

F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.

Other names: Recombinant Human Granulocyte Colony Stimulating Factor (rh G-CSF) Fc fusion protein

EC regimen

Drug

Epirubicin 100 mg/m^2 (in vein) and Cyclophosphamide 600 mg/m^2 (in vein) on Day 1 of each cycle for 4 cycles.

Other names: Epirubicin + Cyclophosphamide

Primary outcomes

  1. Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.

    Time frame: Up to 4 cycles (about 84 days)

    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.

  2. Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.

    Time frame: Up to 21 days

    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).

Secondary outcomes

  1. T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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).

  2. Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  3. Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  4. Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  5. Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  6. Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  7. Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3

    Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)

    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.

  8. Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L)

    Time frame: Up to 4 cycles (84 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.

  9. Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L)

    Time frame: Up to 4 cycles (84 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.

  10. Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days)

    Time frame: Up to 4 cycles (84 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.

  11. Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days)

    Time frame: Up to 4 cycles (84 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.

  12. Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L)

    Time frame: Up to 4 cycles (84 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.

  13. Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir

    Time frame: Up to 4 cycles (84 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.

Sponsors and collaborators

Lead sponsor

EVIVE Biotechnology

Industry

Collaborators

  • Fudan University

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Aug 19, 2015
Registry last updated
Feb 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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