Clinical trial NCT02522234: A Pharmacokinetics/Dynamics Ib Study of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy
Official title: A Phase Ib Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of F-627 as Prophylaxis Therapy to TAC Chemotherapy in Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neutropenia
Keywords: Neutropenia
Chemotherapy
Lead sponsor: EVIVE Biotechnology
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
name: Sun Yat-sen University
First posted: 2015-08-13
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a phase Ib study of the safety and pharmacokinetics/pharmacodynamics of F-627 once per cycle as prophylaxis therapy to chemotherapy in women with breast cancer.

The patients received the intravenous administration of the chemotherapy (docetaxol, doxorubicin and cyclophosphamide, 75 mg/m2, 50 mg/m2 and 500 mg/m2 respectively) on Day 1 and the subcutaneous injection of F-627 at 240 µg/kg and 320 µg/kg on Day 2 (approximately 24 hours after chemotherapy) each cycle for up to 6 cycles.

Detailed description: This study was a phase Ib study of the safety and pharmacokinetics/pharmacodynamics of F-627 once per cycle as prophylaxis therapy to chemotherapy in women with breast cancer.

This study was conducted at two centers in China and enrolled 15 patients with breast cancer receiving TAC chemotherapy (docetaxel, doxorubicin and cyclophosphamide). The patients received the intravenous administration of the chemotherapy (docetaxol, doxorubicin and cyclophosphamide, 75 mg/m2, 50 mg/m2 and 500 mg/m2 respectively) on Day 1 and the subcutaneous injection of F-627 at 240 µg/kg and 320 µg/kg on Day 2 (approximately 24 hours after chemotherapy) each cycle for up to 6 cycles. Patients will remain on study drug dose for each of the following 6 chemotherapy cycles.

Patients will remain on study drug dose for each of the following 6 chemotherapy cycles. The blood sampling will be collected for F-627 serum concentration analysis in cycle of 1 and 3.

Eligibility criteria: Inclusion Criteria:

1. 18-75 years old;
2. Female with breast cancer patients after resection who planned to receive up to 6 cycles of chemotherapy (docetaxol, doxorubicin and cyclophosphamide).
3. Score 0-1 of East Cooperative Oncology Group (ECOG).
4. Absolute neutrophil count (ANC) ≥ 2.0 × 109/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 109/L prior to chemotherapy;
5. Liver and kidney function tests were within normal range;
6. Left ventricular ejection fraction (LVEF) \> 50%;
7. Willing to provide written informed consent and to compliant study procedure.

Exclusion Criteria:

1. Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment.
2. Expected survival \< 12 months.
3. Patients received radiotherapy within 4 weeks prior to enrollment.
4. Patients received neoadjuvant chemotherapy prior to the resection for breast cancer.
5. Patients received bone marrow or hemopoietic stem cell transplantation;
6. Patient was with malignancy other than breast cancer.
7. Patients received G-CSF treatment within 6 weeks prior to enrollment.
8. Patient cann't tolerate the pre-treatment of chemotherapy.
9. Acute congestive heart failure, myocardial disease, or myocardial infarction diagnosed by clinical, electrocardiography, or any other medical procedure.
10. Any disease that possibly cause splenomegaly.
11. 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.
12. 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.
13. Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS).
14. Patients with sickle-cell anemia.
15. Patients with alcohol abuse or drug addiction that may affect the compliance of the study.
16. Patients with allergy to proteins extracted from Escherichia coli, G-CSF, or drug excipient.
17. Patients took other investigational products within 4 weeks prior enrollment.
18. Patients with diseases or symptoms that may not be suitable to be enrolled in this study based on investigator's judgment.

Primary outcomes:
measure: Number of participants with adverse events/abnormal laboratory value as measure of safety
timeFrame: Up to 6 cycles (about 126 days)
Secondary outcomes:
measure: Parameter of Peak Plasma Concentration
timeFrame: Cycle 1 and cycle 3 (each cycle was about 21 days)
measure: Parameter of Area Under Plasma Concentration versus Time Curve
timeFrame: Cycle 1 and cycle 3 (each cycle was about 21 days)
measure: Parameter of Clearance
timeFrame: Cycle 1 and cycle 3 (each cycle was about 21 days)
measure: Absolute Neutrophil Count changes over time
timeFrame: Up to 6 cycles (about 126 days)
Other outcomes:
measure: Immunogenicity of F-627
timeFrame: Up to 6 cycles (about 126 days)
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan Universtiy Shanghai Cancer Center
name: Junning Cao, Professor
role: PRINCIPAL_INVESTIGATOR
References: