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A Pharmacokinetics/Dynamics Ib Study of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

Primary Purpose

Neutropenia

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

F-627 240 μg/kg

F-627 320 μg/kg

About this trial

This is an interventional treatment trial for Neutropenia focused on measuring Neutropenia, Chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

F-627 240 µg/kg

F-627 320 µg/kg

Arm Description

F-627 at the dose of 240 mcg/kg administered by s.c. injection on Day 2 of each cycle for up to 6 cycles. Chemotherapy (docetaxol, doxorubicin and cyclophosphamide) administered by intravenous injection on Day 1 of each cycle for up to 6 cycles.

F-627 at the dose of 320 mcg/kg administered by s.c. injection on Day 2 of each cycle for 6 cycles. Chemotherapy (docetaxol, doxorubicin and cyclophosphamide) administered by intravenous injection on Day 1 of each cycle for up to 6 cycles.

Outcomes

Primary Outcome Measures

Number of participants with adverse events/abnormal laboratory value as measure of safety

Number of participants with adverse events/abnormal laboratory value as measure of safety and tolerability of rh G-CSF Fc fusion protein (F-627) in female patients wiht breast cance receiving adjuvant chemotherapy.

Secondary Outcome Measures

Parameter of Peak Plasma Concentration

Parameter of Peak Plasma Concentration as a measure of pharmacokinetics profile of F-627.

Parameter of Area Under Plasma Concentration versus Time Curve

Parameter of Area Under Plasma Concentration versus Time Curve as a measure of pharmacokinetics profile of F-627.

Parameter of Clearance

Parameter of Clearance as a measure of pharmacokinetics profile of F-627.

Absolute Neutrophil Count changes over time

Absolute Neutrophil Count changes over time as measure of pharmacodynamics of F-627.

Full Information

NCT ID

NCT02522234

First Posted

August 10, 2015

Last Updated

November 19, 2019

Sponsor

EVIVE Biotechnology

Collaborators

Fudan University, Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT02522234

Brief Title

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

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

February 25, 2014 (Actual)

Primary Completion Date

August 19, 2015 (Actual)

Study Completion Date

August 19, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EVIVE Biotechnology

Collaborators

Fudan University, Sun Yat-sen University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neutropenia

Keywords

Neutropenia, Chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

F-627 240 µg/kg

Arm Type

Experimental

Arm Description

Arm Title

F-627 320 µg/kg

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

F-627 240 μg/kg

Other Intervention Name(s)

rh G-CSF Fc Fusion Protein

Intervention Description

F-627 at 240 μg/kg dose enrolling 6 patients with breast cancer receiving adjuvant chemotherapy. Subjects will receive a corresponding dose of F-627 by subcutaneous injection 24 hours after each cycle（21 days） of chemotherapy drug administration. Blood samples are then collected at multiple time points during follow-up visits to evaluate the pharmacokinetics, pharmacodynamics, and safety of the drug. Dose will remain unchanged throughout the treatment period. Eligible subjects will be enrolled sequentially into the 240 μg/kg arm. And the arm should contain 6 evaluable subjects.

Intervention Type

Biological

Intervention Name(s)

F-627 320 μg/kg

Other Intervention Name(s)

rh G-CSF Fc Fusion Protein

Intervention Description

F-627 at 320 μg/kg dose enrolling 6 patients with breast cancer receiving adjuvant chemotherapy. Subjects will receive a corresponding dose of F-627 by subcutaneous injection 24 hours after each cycle（21 days） of chemotherapy drug administration. Blood samples are then collected at multiple time points during follow-up visits to evaluate the pharmacokinetics, pharmacodynamics, and safety of the drug. Dose will remain unchanged throughout the treatment period. Eligible subjects will be enrolled sequentially into the 320 μg/kg arm. The arm should contain 6 evaluable subjects.

Primary Outcome Measure Information:

Title

Number of participants with adverse events/abnormal laboratory value as measure of safety

Description

Time Frame

Up to 6 cycles (about 126 days)

Secondary Outcome Measure Information:

Title

Parameter of Peak Plasma Concentration

Description

Parameter of Peak Plasma Concentration as a measure of pharmacokinetics profile of F-627.

Time Frame

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

Title

Parameter of Area Under Plasma Concentration versus Time Curve

Description

Parameter of Area Under Plasma Concentration versus Time Curve as a measure of pharmacokinetics profile of F-627.

Time Frame

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

Title

Parameter of Clearance

Description

Parameter of Clearance as a measure of pharmacokinetics profile of F-627.

Time Frame

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

Title

Absolute Neutrophil Count changes over time

Description

Absolute Neutrophil Count changes over time as measure of pharmacodynamics of F-627.

Time Frame

Up to 6 cycles (about 126 days)

Other Pre-specified Outcome Measures:

Title

Immunogenicity of F-627

Description

Immunogenicity of F-627 by serum anti-F-627 antibody analysis.

Time Frame

Up to 6 cycles (about 126 days)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 18-75 years old; Female with breast cancer patients after resection who planned to receive up to 6 cycles of chemotherapy (docetaxol, doxorubicin and cyclophosphamide). Score 0-1 of East Cooperative Oncology Group (ECOG). Absolute neutrophil count (ANC) ≥ 2.0 × 109/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 109/L prior to chemotherapy; Liver and kidney function tests were within normal range; Left ventricular ejection fraction (LVEF) > 50%; Willing to provide written informed consent and to compliant study procedure. Exclusion Criteria: Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment. Expected survival < 12 months. Patients received radiotherapy within 4 weeks prior to enrollment. Patients received neoadjuvant chemotherapy prior to the resection for breast cancer. Patients received bone marrow or hemopoietic stem cell transplantation; Patient was with malignancy other than breast cancer. Patients received G-CSF treatment within 6 weeks prior to enrollment. Patient cann't tolerate the pre-treatment of chemotherapy. Acute congestive heart failure, myocardial disease, or myocardial infarction diagnosed by clinical, electrocardiography, or any other medical procedure. Any disease that possibly cause splenomegaly. 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. 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. Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS). Patients with sickle-cell anemia. Patients with alcohol abuse or drug addiction that may affect the compliance of the study. Patients with allergy to proteins extracted from Escherichia coli, G-CSF, or drug excipient. Patients took other investigational products within 4 weeks prior enrollment. Patients with diseases or symptoms that may not be suitable to be enrolled in this study based on investigator's judgment.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Junning Cao, Professor

Organizational Affiliation

Fudan Universtiy Shanghai Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

ZIP/Postal Code

200032

Country

China

12. IPD Sharing Statement

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A Pharmacokinetics/Dynamics Ib Study of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy

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