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NCT Number: NCT04174599

Study to Compare the Efficacy and Safety of F-627 and GRAN®

A Phase III, Multi-Center, Randomized, Open-Label, Active-Controlled Trial to Compare the Efficacy and Safety of Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein (F-627) and Recombinant Human Granulocyte Colony Stimulating Factor (GRAN®) in the Prophylactic Treatment for Chemotherapy-Induced Neutropenia

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

About this study

Study Stage: Phase III

Study Population: Female patients with breast cancer will be enrolled to receive at least 4 cycles of Epirubicin + Cyclophosphamide (EC) chemotherapy, that is: epirubicin 100 mg/m^2 and cyclophosphamide 600 mg/m^2.

Study Design: A multi-center, randomized, open-label, active-controlled phase III clinical trial

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Willing to sign the informed consent form and able to comply with protocol requirements;
  • 18-75 years old;
  • Female postoperative patients with breast cancer who require adjuvant chemotherapy, and are planned to receive at least 4 cycles of EC chemotherapy, namely epirubicin 100 mg/m^2 + cyclophosphamide 600 mg/m^2;
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
  • Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L, hemoglobin (Hb) ≥ 11.0 g/dL, and platelet (PLT) ≥ 100 × 10^9/L prior to enrollment;
  • Hepatic and renal functions: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, serum creatinine ≤ 1.5 × ULN;
  • Left ventricular ejection fraction > 50%;
  • Women without child-bearing potential, i.e., women who have had menopause for at least 1 year or who have undergone sterilization (bilateral tubal ligation, double oophorectomy or hysterectomy); patients with child-bearing potential should agree to take appropriate contraceptive measures, including condoms, spermicidal condoms, foams, gels, contraceptive barrier, intrauterine devices (IUD), and contraceptives (oral or injection), starting from 1 month before the start of the study until 30 days after the end of the study.

Exclusion criteria

  • Radiation therapy within 4 weeks prior to enrollment;
  • Patients with breast cancer who have received neoadjuvant chemotherapy before surgery;
  • Prior bone marrow or stem cell transplant;
  • With other malignant tumors other than breast cancer;
  • Patients who have received a treatment with recombinant human granulocyte colony stimulating factor within 6 weeks prior to randomization;
  • Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, 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;
  • Women in pregnancy or breastfeeding;
  • Known HIV positive or AIDS;
  • With active tuberculosis (TB); history of TB exposure, unless negative for tuberculin test; TB patients undergoing treatment; or suspected TB evaluated by chest x-ray;
  • With sickle cell anemia;
  • With alcohol or drug abuse that may affect the compliance with the study;
  • With known hypersensitivity to granulocyte colony stimulating factor or excipients;
  • Have received any other investigational drug within 1 month or 5 half-lives of the investigational drugs prior to enrollment (whichever is longer);
  • Patients with diseases or symptoms unsuitable for participating in the trial. For example, the study drugs may compromise the health of the patient or the assessment of adverse events may be affected.

Treatment and study plan

F-627

Drug

Day 3 of each cycle, i.e., 48 ± 4 h after starting chemotherapy

Other names: Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein

GRAN®

Drug

Since day 3 of each cycle, i.e., 48 ± 4 h after starting chemotherapy, continuous treatment for ≤ 2 weeks or until ANC recovers to 5.0 × 10^9/L from nadir (investigators may refer to ANC test results from the Department of Laboratory Medicine of each study sites to decide when to discontinue GRAN®)

Other names: Filgrastim

Primary outcomes

  1. Duration of Grade 3 or 4 Neutropenia (ANC <1.0×10^9/L) in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

Secondary outcomes

  1. Number of Participants With Grade 3 or 4 Neutropenia in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L

  2. Number of Participants With Grade 3 or 4 Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L

  3. Number of Participants With Grade 3 or 4 Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L

  4. Number of Participants With Grade 3 or 4 Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L

  5. Duration of Grade 3 or 4 Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  6. Duration of Grade 3 or 4 Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  7. Duration of Grade 3 or 4 Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  8. Number of Participants With Grade 4 Neutropenia in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.

  9. Number of Participants With Grade 4 Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.

  10. Number of Participants With Grade 4 Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.

  11. Number of Participants With Grade 4 Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.

  12. Duration of Grade 4 Neutropenia in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  13. Duration of Grade 4 Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  14. Duration of Grade 4 Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  15. Duration of Grade 4 Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  16. Overall Duration of Grade 3 or 4 Neutropenia in 4 Cycles

    Time frame: Overall 4, 21-day chemotherapy cycles(average 12 weeks)

    Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  17. Number of Participants With Grade 2 or Greater Neutropenia in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L

  18. Number of Participants With Grade 2 or Greater Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L

  19. Number of Participants With Grade 2 or Greater Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L

  20. Number of Participants With Grade 2 or Greater Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L

  21. Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  22. Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  23. Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  24. Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant.

    The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).

  25. The Absolute Neutrophil Counts (ANC) Nadir From Day 3 to Day 13 of Cycle 1

    Time frame: From day 3 to day 13 of cycle 1 (11 days)

    The minimum value of ANC measured from day 3 to day 13 of cycle 1

  26. Number of Participants With Febrile Neutropenia (FN) in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    FN is defined as ANC < 1.0 × 10^9/L with fever (a single measurement of body temperature >38.3 °C or body temperature ≥ 38.0 °C for more than 1 hr).

  27. Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 1

    Time frame: Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

    If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.

  28. Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 2

    Time frame: Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)

    If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.

  29. Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 3

    Time frame: Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)

    If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.

  30. Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 4

    Time frame: Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

    If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.

Sponsors and collaborators

Lead sponsor

EVIVE Biotechnology

Industry

Registry information

Official study title

A Phase III, Multi-Center, Randomized, Open-Label, Active-Controlled Study to Compare the Efficacy and Safety of F-627 and GRAN® in the Prophylactic Treatment for Chemotherapy-Induced Neutropenia

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Nov 22, 2019
Registry last updated
Apr 20, 2025

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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