Back to results

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

Primary Purpose

Neutropenia

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

F-627

Filgrastim

About this trial

This is an interventional treatment trial for Neutropenia focused on measuring Neutropenia, Myelotoxic Chemotherapy, G-CSF

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Willing to provide written informed consent and to compliant study procedure.
18-70 years old;
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).
Score 0-2 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%.
If female, subject is either not of childbearing potential, or is of childbearing potential.

Exclusion Criteria:

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.
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.
Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment.
Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS).
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.
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 1 month or 5 half-lives prior to the enrollment (longer time period is preferred) based on the mechanism of action.
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 3

Arm Type

Experimental

Arm Label

F-627, 10 mg/dose

F-627, 20 mg/dose

Filgrastim, 5 mcg/kg/dose

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

The duration of moderate or severe (grade 3 and 4, respectively) neutropenia

The duration of moderate or severe (grade 3 and 4, respectively) neutropenia post chemotherapy as measure of efficacy of F-627 compared to Filgrastim in female patients wiht breast cance receiving adjuvant chemotherapy.

Secondary Outcome Measures

The incidence rates of Grade 3 and Grade 4 neutropenia

The incidence rates of Grade 3 and Grade 4 neutropenia (ANC < 1.0 × 109/L and < 0.5 × 109/L, respectively) for all chemotherapy cycles.

The duration in days of Grade 3 and Grade 4 neutropenia for cycle 2 to 4.

The duration in days of Grade 3 and Grade 4 neutropenia (ANC <1.0 × 109/L and ANC <0.5 × 109/L, respectively) for cycle 2 to 4.

The incidence rates of febrile neutropenia

The incidence rates of febrile neutropenia (FN; defined as a decrease in neutrophils associated with fever) for each chemotherapy cycle.

The depth of the ANC nadir

The depth of the ANC nadir for chemotherapy Cycles 1 to 4.

Number of participants with adverse events, changes from baseline of laboratory

Number of participants with adverse events, changes from baseline of laboratory values as measure of safety of F-627 compared to Filgrastim in female patients with breast cancer receiving chemotherapy.

Full Information

NCT ID

NCT02521441

First Posted

August 10, 2015

Last Updated

February 22, 2018

Sponsor

EVIVE Biotechnology

Collaborators

Fudan University, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Nanfang Hospital, Southern Medical University, The Affiliated Hospital of Qingdao University, Tongji Hospital, The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China, RenJi Hospital, Zhejiang Cancer Hospital, Yunnan Cancer Hospital, Henan Cancer Hospital, Jiangsu Provincial People's Hospital, Huaxi Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02521441

Brief Title

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

Official Title

A Multi-center, Randomized, Open-label, Active-controlled, Dose Finding Study to Evaluate the Efficacy and Safety of F-627 Compared to Filgrastim in Women With Breast Cancer Receiving Myelotoxic Chemotherapy.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

July 3, 2014 (Actual)

Primary Completion Date

September 20, 2015 (Actual)

Study Completion Date

December 22, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EVIVE Biotechnology

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Neutropenia

Keywords

Neutropenia, Myelotoxic Chemotherapy, G-CSF

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

138 (Actual)

8. Arms, Groups, and Interventions

Arm Title

F-627, 10 mg/dose

Arm Type

Experimental

Arm Description

Arm Title

F-627, 20 mg/dose

Arm Type

Experimental

Arm Description

Arm Title

Filgrastim, 5 mcg/kg/dose

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

F-627

Intervention Description

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

Intervention Name(s)

Filgrastim

Other Intervention Name(s)

rh G-CSF

Intervention Description

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.

Primary Outcome Measure Information:

Title

The duration of moderate or severe (grade 3 and 4, respectively) neutropenia

Description

Time Frame

In first of 4 cycles (21 days for each cycle) 84 days

Secondary Outcome Measure Information:

Title

The incidence rates of Grade 3 and Grade 4 neutropenia

Description

The incidence rates of Grade 3 and Grade 4 neutropenia (ANC < 1.0 × 109/L and < 0.5 × 109/L, respectively) for all chemotherapy cycles.

Time Frame

up to 4 cycles (84 days)

Title

The duration in days of Grade 3 and Grade 4 neutropenia for cycle 2 to 4.

Description

The duration in days of Grade 3 and Grade 4 neutropenia (ANC <1.0 × 109/L and ANC <0.5 × 109/L, respectively) for cycle 2 to 4.

Time Frame

cycle 2-4 (63 days)

Title

The incidence rates of febrile neutropenia

Description

The incidence rates of febrile neutropenia (FN; defined as a decrease in neutrophils associated with fever) for each chemotherapy cycle.

Time Frame

Up to 4 cycles (84 days)

Title

The depth of the ANC nadir

Description

The depth of the ANC nadir for chemotherapy Cycles 1 to 4.

Time Frame

Up to 4 cycles (84 days)

Title

Number of participants with adverse events, changes from baseline of laboratory

Description

Time Frame

Up to 4 cycles (84 days)

Other Pre-specified Outcome Measures:

Title

Immunogenicity of F-627

Description

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

Time Frame

Up to 4 cycles (84 days)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing to provide written informed consent and to compliant study procedure. 18-70 years old; 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). Score 0-2 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%. If female, subject is either not of childbearing potential, or is of childbearing potential. Exclusion Criteria: 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. 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. Pregnancy or lactating women; female with pregnancy potential had positive pregnancy test prior to study treatment. Known the positive result of human immunodeficiency virus (HIV) or patients with acquired immune deficiency syndrome (AIDS). 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. 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 1 month or 5 half-lives prior to the enrollment (longer time period is preferred) based on the mechanism of action. 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

Jin Li, Professor

Organizational Affiliation

Fudan University

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs