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Intermittent G-CSF in Patients With Breast Cancer Receiving Adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)

Primary Purpose

Breast Cancer, Neutropenia, Febrile Neutropenia

Status
Terminated
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Filgrastim
Peg-filgrastim
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring Breast cancer, Adjuvant, Docetaxel, Adriamycin, Cyclophosphamide, Neutropenia, Filgrastim, Pegfilgrastim

Eligibility Criteria

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

Inclusion Criteria:

  • The patients who underwent surgery for pathologically diagnosed early breast cancer (high risk stage II or stage III) or completely resected stage IV, and anticipated to undergo adjuvant chemotherapy with TAC regimen (docetaxel, doxorubicin, and cyclophosphamide)
  • The patients satisfying laboratory findings below before the enrollment of clinical trials: A. Absolute Neutrophil Count(ANC) ≥ 1,500/mm³; B. Platelet Count ≥ 100,000/mm³; C. Adequate renal functions (Cr < 1.5 X ULN); and D. Adequate liver function (Bilirubin < 1.5 X ULN, AST/ALT < 2.5 X ULN)
  • ECOG Performance status: 0-1
  • Cardiac ejection fraction ≥ 50% as measured by MUGA or 2D echocardiography without clinically significant abnormalities
  • Voluntarily participated in this study, and written informed consent of the patient

Exclusion Criteria:

  • Past history of immunotherapy or chemotherapy
  • Past history of autologous stem cell transplantation or bone marrow transplantation
  • The patient undergone radiation therapy within 4 weeks after written informed consent
  • Patient with any other concurrent malignancies or who are currently cured with past history within 5 years (excluding completely resected stage I early skin cancer)
  • Pregnant or lactating women, women of childbearing potential not employing adequate contraception
  • Other serious illness or medical conditions inadequate to chemotherapy: A. Unstable cardiac disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry; B. History of significant neurological or psychiatric disorders including dementia or seizures; Active uncontrolled infection (viral, bacterial or fungal infection); and D. Other serious medical illnesses
  • Known hypersensitivity to any of the study drugs or its ingredients
  • Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.
  • Past history of usage of granulocyte-colony stimulating factors
  • Patients with a known history of HIV (+) or HCV (+). However, HBV(+) patients who undergo primary prophylaxis are eligible.
  • Other serious illness or medical conditions determined by investigator

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A. Pegfilgrastim

B. Filgrastim

Arm Description

D2 once a cycle pegfilgrastim arm

Intermittent Every Other Days of 5 Shot (D3-11) filgrastim arm

Outcomes

Primary Outcome Measures

Cumulative incidence of febrile neutropenia
Measured at the completion of cycle 3

Secondary Outcome Measures

Incidence of febrile neutropenia at each cycle
Measured at the completion of each cycle 1, 2, and 3
Rates of anti-microbial use
Measured at the completion of cycle 3
Duration of anti-microbial use
Measured at the completion of cycle 3
Cumulative dose of chemotherapeutic agents
Measured at the completion of cycle 3
Delay rate of next chemotherapy cycle due to inadequate neutrophil recovery
Measured at the completion of each cycle 1, 2, and 3
Duration of delay of next chemotherapy cycle due to inadequate neutrophil recovery
Measured at the completion of each cycle 1, 2, and 3

Full Information

First Posted
February 10, 2016
Last Updated
July 29, 2020
Sponsor
Asan Medical Center
Collaborators
Kyowa Kirin Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02685111
Brief Title
Intermittent G-CSF in Patients With Breast Cancer Receiving Adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)
Official Title
Intermittent Every Other Days of 5 Shot-filgrastim Compared With Single Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide Chemotherapy (Intermittent G-CSF 105)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Study Start Date
February 2016 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Kyowa Kirin Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
To compare the efficacy and safety of Day 2 (D2) once a cycle pegfilgrastim with Intermittent Every Other Days of 5 Shot (D3-11) filgrastim in early breast cancer patients treated with adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) regimen
Detailed Description
According to manufacturers' recommendations (Amgen: Neupogenᵀᴹ), filgrastim are to start 24 hrs after the last dose of chemotherapy and continue until absolute neutrophil count (ANC) has recovered to within the normal range (or for 14 days). However, for economic and practical reasons and/or patient's convenience, it has been common practice to initiate filgrastim at a later days of cycle and/or administer a shorter course of treatment. Data from several clinical studies have shown that 10-11 days' filgrastim treatment is required for optimal prophylaxis for febrile neutropenia (FN), and data from other cancers shows that suboptimal use of G-CSFs could deteriorate clinical outcomes. However, in two recent randomized study with breast cancer patients undergoing TAC chemotherapy, acceptable incidence (7-18%) of FN was shown with the consecutive 6 or 7-daily filgrastim schemes. Also, although there is theoretical concern that there can be wide fluctuations in the patient's ANC over time in alternate or intermittent filgrastim administration, because there was no difference in clinical outcomes between daily- or intermittent-dose filgrastim schedules in previous literatures, the intermittent every other day of 5 shot-filgrastim scheme would have clinical outcomes comparable with previous consecutive 6 or 7-daily filgrastim schemes in coverage of ANC nadir. Therefore, it can be justified to investigate the non-inferiority of intermittent every other days of 5 shot-filgrastim scheme compared with control arm using of pegfilgrastim on D2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Neutropenia, Febrile Neutropenia
Keywords
Breast cancer, Adjuvant, Docetaxel, Adriamycin, Cyclophosphamide, Neutropenia, Filgrastim, Pegfilgrastim

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A. Pegfilgrastim
Arm Type
Active Comparator
Arm Description
D2 once a cycle pegfilgrastim arm
Arm Title
B. Filgrastim
Arm Type
Experimental
Arm Description
Intermittent Every Other Days of 5 Shot (D3-11) filgrastim arm
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
Grasinᵀᴹ pfs inj.
Intervention Description
Filgrastim (Gracinᵀᴹ) is administered at the D3, D5, D7, D9, and D11 of each cycle. A dose of 5 μg/kg/day filgrastim is administered S.C. either as a bolus injection or as a continuous injection. Administer into the outer upper arm, abdomen (except within 2 inches of navel), front middle thigh, or the upper outer buttocks area.
Intervention Type
Drug
Intervention Name(s)
Peg-filgrastim
Other Intervention Name(s)
Neulastaᵀᴹ pfs inj. 6mg/0.6ml
Intervention Description
Pegfilgrastim (Neulastaᵀᴹ) is administered at the D2 of each cycle. A dose of 6mg once a cycle is administered S.C., 24 (± 2) hours after completion of chemotherapy.
Primary Outcome Measure Information:
Title
Cumulative incidence of febrile neutropenia
Description
Measured at the completion of cycle 3
Time Frame
through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Secondary Outcome Measure Information:
Title
Incidence of febrile neutropenia at each cycle
Description
Measured at the completion of each cycle 1, 2, and 3
Time Frame
At each cycle 1, 2, and 3 (each cycle is 21 days)
Title
Rates of anti-microbial use
Description
Measured at the completion of cycle 3
Time Frame
through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Title
Duration of anti-microbial use
Description
Measured at the completion of cycle 3
Time Frame
through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Title
Cumulative dose of chemotherapeutic agents
Description
Measured at the completion of cycle 3
Time Frame
through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Title
Delay rate of next chemotherapy cycle due to inadequate neutrophil recovery
Description
Measured at the completion of each cycle 1, 2, and 3
Time Frame
At each cycle 1, 2, and 3 (each cycle is 21 days)
Title
Duration of delay of next chemotherapy cycle due to inadequate neutrophil recovery
Description
Measured at the completion of each cycle 1, 2, and 3
Time Frame
At each cycle 1, 2, and 3 (each cycle is 21 days)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patients who underwent surgery for pathologically diagnosed early breast cancer (high risk stage II or stage III) or completely resected stage IV, and anticipated to undergo adjuvant chemotherapy with TAC regimen (docetaxel, doxorubicin, and cyclophosphamide) The patients satisfying laboratory findings below before the enrollment of clinical trials: A. Absolute Neutrophil Count(ANC) ≥ 1,500/mm³; B. Platelet Count ≥ 100,000/mm³; C. Adequate renal functions (Cr < 1.5 X ULN); and D. Adequate liver function (Bilirubin < 1.5 X ULN, AST/ALT < 2.5 X ULN) ECOG Performance status: 0-1 Cardiac ejection fraction ≥ 50% as measured by MUGA or 2D echocardiography without clinically significant abnormalities Voluntarily participated in this study, and written informed consent of the patient Exclusion Criteria: Past history of immunotherapy or chemotherapy Past history of autologous stem cell transplantation or bone marrow transplantation The patient undergone radiation therapy within 4 weeks after written informed consent Patient with any other concurrent malignancies or who are currently cured with past history within 5 years (excluding completely resected stage I early skin cancer) Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions inadequate to chemotherapy: A. Unstable cardiac disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry; B. History of significant neurological or psychiatric disorders including dementia or seizures; Active uncontrolled infection (viral, bacterial or fungal infection); and D. Other serious medical illnesses Known hypersensitivity to any of the study drugs or its ingredients Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy. Past history of usage of granulocyte-colony stimulating factors Patients with a known history of HIV (+) or HCV (+). However, HBV(+) patients who undergo primary prophylaxis are eligible. Other serious illness or medical conditions determined by investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sung-Bae Kim, Ph.D.
Organizational Affiliation
Department of Oncology, Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-746
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Intermittent G-CSF in Patients With Breast Cancer Receiving Adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)

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