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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02685111
• Other study ID #: AMC 2015-1143
• Status: Terminated
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: December 2017

Study information

• Verified date: July 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Febrile Neutropenia
• Neutropenia

Intervention

Drug:
• Filgrastim
Filgrastim (Gracin??) 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.
• Peg-filgrastim
Pegfilgrastim (Neulasta??) 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.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Kyowa Kirin Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P, Siena S, Lalisang RI, Samonigg H, Clemens MR, Zani V, Liang BC, Renwick J, Piccart MJ; International Pegfilgrastim 749 Study Group. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol. 2003 Jan;14(1):29-35. — View Citation

Holmes FA, Jones SE, O'Shaughnessy J, Vukelja S, George T, Savin M, Richards D, Glaspy J, Meza L, Cohen G, Dhami M, Budman DR, Hackett J, Brassard M, Yang BB, Liang BC. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002 Jun;13(6):903-9. — View Citation

Koumakis G, Vassilomanolakis M, Barbounis V, Hatzichristou E, Demiri S, Plataniotis G, Pamouktsoglou F, Efremidis AP. Optimal timing (Preemptive versus supportive) of granulocyte colony-stimulating factor administration following high-dose cyclophosphamide. Oncology. 1999;56(1):28-35. — View Citation

Martín M, Lluch A, Seguí MA, Ruiz A, Ramos M, Adrover E, Rodríguez-Lescure A, Grosse R, Calvo L, Fernandez-Chacón C, Roset M, Antón A, Isla D, del Prado PM, Iglesias L, Zaluski J, Arcusa A, López-Vega JM, Muñoz M, Mel JR. Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol. 2006 Aug;17(8):1205-12. Epub 2006 Jun 9. — View Citation

Papaldo P, Lopez M, Marolla P, Cortesi E, Antimi M, Terzoli E, Vici P, Barone C, Ferretti G, Di Cosimo S, Carlini P, Nisticò C, Conti F, Di Lauro L, Botti C, Di Filippo F, Fabi A, Giannarelli D, Calabresi F. Impact of five prophylactic filgrastim schedules on hematologic toxicity in early breast cancer patients treated with epirubicin and cyclophosphamide. J Clin Oncol. 2005 Oct 1;23(28):6908-18. Epub 2005 Aug 29. — View Citation

Scott SD, Chrischilles EA, Link BK, Delgado DJ, Fridman M, Stolshek BS. Days of prophylactic filgrastim use to reduce febrile neutropenia in patients with non-Hodgkin's lymphoma treated with chemotherapy. J Manag Care Pharm. 2003 Mar-Apr;9(2 Suppl):15-21. — View Citation

von Minckwitz G, Kümmel S, du Bois A, Eiermann W, Eidtmann H, Gerber B, Hilfrich J, Huober J, Costa SD, Jackisch C, Grasshoff ST, Vescia S, Skacel T, Loibl S, Mehta KM, Kaufmann M; German Breast Group. Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. Ann Oncol. 2008 Feb;19(2):292-8. Epub 2007 Sep 9. — View Citation

von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005 Apr 20;23(12):2676-85. — View Citation

Weycker D, Hackett J, Edelsberg JS, Oster G, Glass AG. Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization? Ann Pharmacother. 2006 Mar;40(3):402-7. Epub 2006 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of febrile neutropenia	Measured at the completion of cycle 3	through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Secondary	Incidence of febrile neutropenia at each cycle	Measured at the completion of each cycle 1, 2, and 3	At each cycle 1, 2, and 3 (each cycle is 21 days)
Secondary	Rates of anti-microbial use	Measured at the completion of cycle 3	through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Secondary	Duration of anti-microbial use	Measured at the completion of cycle 3	through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Secondary	Cumulative dose of chemotherapeutic agents	Measured at the completion of cycle 3	through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks
Secondary	Delay rate of next chemotherapy cycle due to inadequate neutrophil recovery	Measured at the completion of each cycle 1, 2, and 3	At each cycle 1, 2, and 3 (each cycle is 21 days)
Secondary	Duration of delay of next chemotherapy cycle due to inadequate neutrophil recovery	Measured at the completion of each cycle 1, 2, and 3	At each cycle 1, 2, and 3 (each cycle is 21 days)