A Study Comparing Pegylated Filgrastim and Filgrastim in Support for Chemotherapy

Cancer Clinical Trial

Official title:

A Multicenter, Randomized, Cross-over Phase 3 Comparing Preventive Pegylated Filgrastim and Filgrastim in Cancer Patients Receiving Myelosuppressive Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285219
• Other study ID #: PEG3
• Secondary ID: 2002SL0047
• Status: Completed
• Phase: Phase 3
• First received: January 24, 2011
• Last updated: January 26, 2011
• Start date: January 2006
• Est. completion date: December 2008

Study information

• Verified date: January 2011
• Source: Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Neutropenia is one of the most frequent adverse effects of chemotherapy, and the main factor to limit the dosage and delay the schedule of chemotherapy. Preventive filgrastim administration has long been established as the standard of care. A pegylated filgrastim was independently developed by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China. It composed of filgrastim and a 20 kd polyethylene glycol molecule covalently bound at the N-terminal residue. Preclinical studies phase 1 and phase 2 trials have shown that pegylated filgrastim has decreased renal clearance, increased plasma half-life, and prolonged efficacy in compare with filgrastim. These characters were similar to those of Neulasta.

The investigators designed a multicenter, randomized, cross-over phase Ⅲ trial to compare the efficacy and safety of a single injection of pegylated filgrastim and daily injections of filgrastim in chemotherapy naive patients receiving commonly used regimens. The hypothesis is that pegylated filgrastim is similarly effective and safe with regular filgrastim.

Description:

This was a multicenter, randomized, open-label, cross-over, noninferiority study to evaluate whether a single injection of pegfilgrastim is as effective and safe as daily injections of filgrastim in patients receiving commonly used chemotherapy regimens. Patients were randomly assigned in a 1:1 ratio to AOB and BOA arm with center as the stratification variables. All the patients received two cycles of chemotherapy of identical regimen and dosage. In arm AOB, patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5 ug/kg/d in cycle 2; while in arm BOA, patients received filgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2.

Study drugs Both filgrastim and pegylated filgrastim were provided by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China.

In cycle 1 of AOB arm and cycle 2 of BOA arm, on 9 am of day 3, patients were to receive a dose of 100µg/kg of pegylated filgrastim, based on actual body weight, as a single s.c. injection.

In cycle 2 of AOB arm and cycle 1 of BOA arm, patients were to receive daily s.c. injection of filgrastim at a dose of 5 µg/kg/day. Injections began on 9 am of day 3 and continued daily until an absolute neutrophil count (ANC) ≥10.0 × 109 /l was documented after the expected nadir or for a maximum of 14 days, whichever occurred first.

Chemotherapy Treatment All cytotoxic agents were administrated on day 1 of the 21-day regimens. The regimens include PC(paclitaxel 175 mg/m2; carboplatin area under curve[AUC] 5～6 or cisplatin 75 mg/m2 )； AC (doxorubicin [or pirarubicin]60 mg/m2 or epirubicin 100 mg/m2；cyclophosphamide 600 mg/m2), PA(paclitaxel 175 mg/m2 ；doxorubicin [or pirarubicin]50 mg/m2 or epirubicin 80 mg/m2）； CHOP (cyclophosphamide 750mg/m2；doxorubicin[or pirarubicin] 50 mg/m2 or epirubicin100 mg/m2；vincristine1.4 mg/m2；prednisone 100mg，po，day 1-5)。 Efficacy measurements Blood samples were collected for complete blood counts (cbc) with differential on days 0, 3, 5, 7, 9, 11, 13, 17 and 21 of each cycle. Day 0 was defined as the day before day one, in cycle 1 it is the base line, and in cycle 2 is day 21 of cycle 1.

The primary efficacy end point was protective rate of grade 4 neutropenia after chemotherapy (defined as the rate of ANC keeps above 0.5 × 109 /l through the whole cycle). The secondary efficacy end points included the rate of grade 3/4 neutropenia, time to neutrophil recovery (defined as the time from chemotherapy administration until the patient's ANC increased to 2.0 × 109/l after the expected nadir), incidence of febrile neutropenia (defined as ANC<0.5×109/L and auxiliary temperature>38.0℃), incidence of antibiotic administration and ANC profile.

Safety assessments Patients recorded their auxiliary temperature daily, and were monitored for adverse events throughout the study. Before chemotherapy and in the third week of each chemotherapy cycle, serum hepatic and renal function, electrolysis, urine routine test and electrocardiograph were examined.

The safety endpoint of this study was incidence and severity of adverse events (WHO grade 1-4), side effects, and changes in clinical laboratory values.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 337
• Est. completion date: December 2008
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• diagnosis of malignant solid tumours (excluding highly aggressive lymphomas such as lymphoblastic lymphoma and Burkitt lymphoma)

• chemotherapy naive

• Karnofsky Performance Status =70

• age 18-70 years; normal white blood cell (WBC) count and platelet count

• adequate renal, hepatic and cardiac function

• life expectancy =3 months

• normal bone marrow function

Exclusion Criteria:

• history of systematic chemotherapy (including adjuvant therapy)

• large area radiotherapy (>25% of bone marrow volume)

• uncontrolled infection

• bone marrow involvement

• pregnancy, lactation

• history of blood stem cell or organ transplantation

• antibiotic administration within 72 hours of enrolment

• long time exposure to glucocorticoids and immunosuppressive agents

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• pegylated filgrastim and ?lgrastim
patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and ?lgrastim 5 ug/kg/d in cycle 2
• ?lgrastim and pegylated filgrastim
patients received ?lgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2

Locations

Country	Name	City	State
n/a

Sponsors (15)

Lead Sponsor

Collaborator

Chinese Academy of Medical Sciences

Beijing Chest Hospital, First Hospital of China Medical University, Fudan University, Fujian Cancer Hospital, Hospital affiliated to Academy of Military Medical Sciences, Hunan Cancer Hospital, Peking University Third Hospital, Qilu Hospital, The Second Affiliated Hospital of Dalian Medical University, Tianjin Medical University Cancer, Tianjin People's Hospital, West China Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Zhejiang Cancer Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Protective rate of grade 4 neutropenia	the rate of ANC keeps above 0.5 × 109 /l through the whole cycle	21 days	No
Secondary	rate of grade 3/4 neutropenia	the rate of ANC lower than 1.0 × 109 /l	21 days	No
Secondary	time to neutrophil recovery	the time from chemotherapy administration until the patient's ANC increased to 2.0 × 109/l after the expected nadir	21 days	No
Secondary	incidence of antibiotic administration	rate of using antibiotic in a cycle	21 days	No
Secondary	ANC profile	the dynamic change of ANC number	21 days	No
Secondary	incidence and severity adverse events	unexpected and untoward events	21 days	Yes
Secondary	incidence and severity of side effects	expected and untoward events caused by study drug or control drug	21 days	Yes
Secondary	changes in clinical laboratory values	changes in clinical laboratory values	21 days	Yes
Secondary	incidence of febrile neutropenia	rate of ANC<0.5×109/L and auxiliary temperature>38.0?	21 days	No

External Links

•   GCP center of Cancer Hospital, CAMS