Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy

Breast Neoplasms Clinical Trial

— NEUTHREE  

Official title:

Reducing Neutropenia Incidence by Changing the Date of Eflapegrastim Administration in Breast Cancer Patients Who Have Experienced Neutropenia After Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05949333
• Other study ID #: GGAH 2022-10
• Status: Recruiting
• Phase: Phase 4
• Start date: November 7, 2023
• Est. completion date: July 2025

Study information

• Verified date: February 2024
• Source: Eunseong Medical Foundation Good GANG-AN HOSPITAL
• Contact: Chief of Breast Center
• Phone: 82519338719
• Email: s8668s[@]hanmail.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients who experienced neutropenia after receiving pegfilgrastim on day 1 of the first round are randomly assigned to either the control or experimental arm. Patients in the control arm continue pegfilgrastim injection on day 1 while patients in the experimental arm will receive pegfilgrastim injection on day 3 to see if changing the pegfilgrastim administration date from day 1 to day 3 starting from the second round of chemotherapy could reduce the incidence of neutropenia

Description:

The use of pegfilgrastim, which has a long-lasting effect in the human body, after myelosuppressive chemotherapy for solid tumors, including breast cancer, and blood cancers has led to a decrease in the incidence of neutropenia, including febrile neutropenia, and a reduction in medical costs by shortening hospitalization periods related to side effects of chemotherapy. During the early stages of drug development, there was controversy over the timing of pegfilgrastim administration, and attempts were made to administer it at various times, from the day of chemotherapy to the day of neutropenia began. However, based on several studies, it is now known that patients who receive pegfilgrastim on the day of chemotherapy or after 4 days of chemotherapy have a higher incidence of febrile neutropenia. Therefore, administering pegfilgrastim on day 1-3 after chemotherapy is ideal, but in reality, it is often difficult for patients to visit the hospital multiple times after chemotherapy, so many patients are discharged after receiving pegfilgrastim on day 1. The FDA and National Comprehensive Cancer Network (NCCN) guidelines also recommend administration on day 1. It is known that patients who experience neutropenia after the first round of chemotherapy are more likely to experience it again in subsequent rounds. The investigators aimed to see whether changing the pegfilgrastim administration date from day 1 to day 3 starting from the second round of chemotherapy for patients who experienced neutropenia after receiving pegfilgrastim on day 1 of the first round can reduce the incidence of neutropenia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Women aged 18 to 75 years old as of the date of study registration.
• Patients with histologically confirmed invasive adenocarcinoma.
• Patients with confirmed estrogen receptor, progesterone receptor, and Her2 receptor status.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Patients with a left ventricular ejection fraction (LVEF) =55%.
• Patients who have agreed to participate in this trial and have provided written consent.

Exclusion Criteria:

• Patients with a history of breast cancer treatment
• Patients with a history of chemotherapy, radiation therapy, immunotherapy, or biotherapy for malignancies other than breast cancer
• Patients with infectious diseases
• Patients with serious illnesses that may affect this clinical trial: cardiovascular disease, kidney disease, liver disease, endocrine disease, tumors, or diabetes
• Other individuals deemed by the clinical trial investigators to be unable to participate in the trial.

Related Conditions & MeSH terms

• Breast Neoplasms
• Neutropenia

Intervention

Drug:
• Eflapegrastim
long-acting granulocyte-colony stimulating factor

Locations

Country	Name	City	State
Korea, Republic of	Good Gang-An Hospital	Busan

Sponsors (2)

Lead Sponsor	Collaborator
Eunseong Medical Foundation Good GANG-AN HOSPITAL	Hanmi Pharmaceutical Company Limited

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (10)

Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002 Mar 15;34(6):730-51. doi: 10.1086/339215. Epub 2002 Feb 13. No abstract available. — View Citation

Kaufman PA, Paroly W, Rinaldi D. Randomized double blind phase 2 study evaluating same-day vs. next-day administration of pegfilgrastim with docetaxel, doxorubicin and cyclophosphamide (TAC) in women with early stage and advanced breast cancer. Breast Cancer Res Treat 2004;88:S59.

Leonard RC, Miles D, Thomas R, Nussey F; UK Breast Cancer Neutropenia Audit Group. Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients. Br J Cancer. 2003 Dec 1;89(11):2062-8. doi: 10.1038/sj.bjc.6601279. — View Citation

Lyman GH, Allcott K, Garcia J, Stryker S, Li Y, Reiner MT, Weycker D. The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review. Support Care Cancer. 2017 Aug;25(8):2619-2629. doi: 10.1007/s00520-017-3703-y. Epub 2017 May 8. — View Citation

Meropol NJ, Miller LL, Korn EL, Braitman LE, MacDermott ML, Schuchter LM. Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy. J Natl Cancer Inst. 1992 Aug 5;84(15):1201-3. doi: 10.1093/jnci/84.15.1201. No abstract available. — View Citation

Rowinsky EK, Grochow LB, Sartorius SE, Bowling MK, Kaufmann SH, Peereboom D, Donehower RC. Phase I and pharmacologic study of high doses of the topoisomerase I inhibitor topotecan with granulocyte colony-stimulating factor in patients with solid tumors. J Clin Oncol. 1996 Apr;14(4):1224-35. doi: 10.1200/JCO.1996.14.4.1224. — View Citation

Saven A, Schwartzberg L, Kaywin P, et al. Randomized, double-blind, phase 2, study evaluating same-day vs next-day administration of pegfilgrastim with R-CHOP in non-Hodgkin's lymphoma patients. J ClinOncol2006;24:7570.

Tamura K. Clinical guidelines for the management of neutropenic patients with unexplained fever in Japan: validation by the Japan Febrile Neutropenia Study Group. Int J Antimicrob Agents. 2005 Dec;26 Suppl 2:S123-7; discussion S133-40. doi: 10.1016/j.ijantimicag.2005.08.001. Epub 2005 Oct 24. — View Citation

Weycker D, Bensink M, Lonshteyn A, Doroff R, Chandler D. Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015. Curr Med Res Opin. 2017 Dec;33(12):2107-2113. doi: 10.1080/03007995.2017.1386858. Epub 2017 Oct 16. — View Citation

Weycker D, Li X, Tzivelekis S, Atwood M, Garcia J, Li Y, Reiner M, Lyman GH. Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor. Support Care Cancer. 2017 Feb;25(2):439-447. doi: 10.1007/s00520-016-3421-x. Epub 2016 Oct 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of severe neutropenia Incidence rate of severe neutropenia	The incidence rates of Grade 4 neutropenia (ANC < 500 respectively)	cycle 2-5 (21 days for each cycle), 105 days
Secondary	Duration of severe neutropenia	number of consecutive days ANC lower than 500	cycle 2-5 (21 days for each cycle), 105 days
Secondary	Incidence rate of febrile neutropenia	Severe neutropenia with fever. Fever is defined as below; 37.5? single axillary temperature; 38.0? single ear probe temperature; 38.3? single oral temperature; 38.0? oral temperature over 1 hour in the absence of an obvious cause	cycle 2-5 (21 days for each cycle), 105 days
Secondary	Incidence rate of neutropenia related death	Death related chemotherapy induced neutropenia sepsis	1 year