A Phase II, Dose-finding Study of F-627 in Patients With Breast Cancer Receiving Myelotoxic Chemotherapy.

NCT ID: NCT02521441

Last Updated: 2018-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-03
• Study Completion Date: 2015-12-22

Brief Summary

This was a randomized, open-label, active-controlled, dose-finding, phase II study to evaluate the efficacy and safety of 2 doses of F-627 compared to Filgrastim in women with breast cancer receiving myelotoxic chemotherapy.

Subjects would be randomized to one of three arms, which were 10 mg/dose of F-627, 20 mg/dose of F-627 or Filgrastim, in an equal ratio.

Detailed Description

This phase II study was conducted at 16 clinical centers in China and planned to enroll 150 women with breast cancer who will receive chemotherapy that includes up to 4 cycles of epirubicin and cyclophosphamide, 100 mg/m2 and 600 mg/m2, respectively. Subjects would be randomized to one of three arms, which were 10 mg/dose of F-627, 20 mg/dose of F-627 or Filgrastim, in an equal ratio on Day 1 of the study. Patients will remain on their randomized study drug dose and regimen for each of the following 3 chemotherapy cycles. The chemotherapy to be administered for chemotherapy cycles 2-4 should be the same therapy administered to the subject on Day1.

Chemotherapy will be administrated through intravenous IV) injection on Day 1 of each 21-day cycle and be repeated every 3 weeks for up to four cycles unless a dose delay is necessary. Approximately 48 hours after chemotherapy completion in cycle (day 3 of the cycle), patients will either receive a subcutaneous (SC) injection of F-627 (either 10 mg/dose or 20 mg/dose) or 5 μg/kg/dose filgrastim used up to two weeks or stopped while ANC more than 5 × 109/L.

To track ANC concentration post chemotherapy, subjects returned to their study site for blood draws either daily (Cycle 1) or 3 times per week (every other day; Cycles 2-4) until ANC levels reached ≥2.0 × 109/L, post-nadir, and then every 3 days until the next chemotherapy cycle.

All subjects returned for an End of Study visit approximately 3 weeks after their final study drug administration (Study Day 84) and had a follow-up phone call 30 days after the last study drug.

Conditions

Neutropenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

F-627, 10 mg/dose

F-627 at dose of 10 mg/dose administered by subcutaneous injection on Day 3 of each cycle for up to 4 cycles. EC regimen (Epirubicin and Cyclophosphamide) administered by intravenous injection on Day 1 of each cycle for 4 cycles.

Group Type: EXPERIMENTAL

F-627

Intervention Type: BIOLOGICAL

F-627 at doses of 10 mg/dose or 20 mg/dose, s.c. on Day 3 of each cycle for up to 4 cycles.

F-627, 20 mg/dose

F-627 at dose of 20 mg/dose administered by subcutaneous injection on Day 3 of each cycle for up to 4 cycles. EC regimen (Epirubicin and Cyclophosphamide) administered by intravenous injection on Day 1 of each cycle for 4 cycles.

Group Type: EXPERIMENTAL

F-627

Intervention Type: BIOLOGICAL

F-627 at doses of 10 mg/dose or 20 mg/dose, s.c. on Day 3 of each cycle for up to 4 cycles.

Filgrastim, 5 mcg/kg/dose

Filgrastim of 5 mcg/dose administered by subcutaneous injection for up to two weeks, start from Day 3 of each cycle for up to 4 cycles. EC regimen (Epirubicin and Cyclophosphamide) administered by intravenous injection on Day 1 of each cycle for 4 cycles.

Group Type: EXPERIMENTAL

Filgrastim

Intervention Type: BIOLOGICAL

Filgrastim at dose of 5 mcg/kg/day for up to 2 weeks, s.c. start from Day 3 of each cycle for up to 4 cycles.

Interventions

F-627

F-627 at doses of 10 mg/dose or 20 mg/dose, s.c. on Day 3 of each cycle for up to 4 cycles.

Intervention Type: BIOLOGICAL

Filgrastim

Filgrastim at dose of 5 mcg/kg/day for up to 2 weeks, s.c. start from Day 3 of each cycle for up to 4 cycles.

Intervention Type: BIOLOGICAL

Other Intervention Names

rh G-CSF

Eligibility Criteria

Inclusion Criteria

1. Willing to provide written informed consent and to compliant study procedure.

2. 18-70 years old;

3. Female with breast cancer patients after resection who planned to receive up to 4 cycles of chemotherapy (epirubicin and cyclophosphamide, 100 mg/m2 and 600 mg/m2, respectively).

4. Score 0-2 of East Cooperative Oncology Group (ECOG).

5. Absolute neutrophil count (ANC) ≥ 2.0 × 109/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 109/L prior to chemotherapy.

6. Liver and kidney function tests were within normal range.

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

8. If female, subject is either not of childbearing potential, or is of childbearing potential.

Exclusion Criteria

1. Patients received radiotherapy within 4 weeks prior to enrollment.

2. Patients received neoadjuvant chemotherapy prior to the resection for breast cancer.

3. Patients received bone marrow or hemopoietic stem cell transplantation.

4. Patient was with malignancy other than breast cancer.

5. Patients received G-CSF treatment within 6 weeks prior to enrollment.

6. Acute congestive heart failure, myocardial disease, or myocardial infarction diagnosed by clinical, electrocardiography, or any other medical procedure.

7. Any disease that possibly cause splenomegaly.

8. 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.

9. Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment.

10. Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS).

11. 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.

12. Patients with sickle-cell anemia.

13. Patients with alcohol abuse or drug addiction that may affect the compliance of the study.

14. Patients with allergy to proteins extracted from Escherichia coli, G-CSF, or drug excipient.

15. Patients took other investigational products within 1 month or 5 half-lives prior to the enrollment (longer time period is preferred) based on the mechanism of action.

16. Patients with diseases or symptoms that may not be suitable to be enrolled in this study based on investigator's judgment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: collaborator

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: collaborator

The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China

OTHER

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

Yunnan Cancer Hospital

OTHER

Sponsor Role: collaborator

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Jiangsu Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Huaxi Hospital

OTHER

Sponsor Role: collaborator

EVIVE Biotechnology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Li, Professor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Countries

China

References

Ji D, Wang S, Yao W, Hou D, Wang X, Ye C, Li H, Yang H, Yi J, Lu J, Wang H, Xu X, Cai D, Liu X, Yan X, Nie J, Cui S, Jiang H, Cao J. Efbemalenograstim Alfa, an Fc Fusion Protein, Long-Acting Granulocyte Colony-Stimulating Factor for Reducing the Risk of Chemotherapy-Induced Neutropenia: Results of a Phase II Randomized, Multicenter, Open-Label Trial. Clin Drug Investig. 2025 Oct 9. doi: 10.1007/s40261-025-01479-y. Online ahead of print.

Reference Type: DERIVED

PMID: 41066031 (View on PubMed)

Other Identifiers

SP-CDR-1-1302

Identifier Type: -

Identifier Source: org_study_id