A Study Comparing Pegylated Filgrastim and Filgrastim in Support for Chemotherapy

This study has been completed.
Sponsor:
Collaborators:
Fujian Cancer Hospital
Beijing Chest Hospital
Hospital affiliated to Academy of Military Medical Sciences
Tianjin Medical University Cancer
Fudan University
China Medical University, China
Hunan Cancer Hospital
West China Hospital
Second Affiliated Hospital of Dalian Medical University
Peking University Third Hospital
Tianjin People's Hospital
Qilu Hospital
Zhejiang Cancer Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Information provided by:
Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01285219
First received: January 24, 2011
Last updated: January 26, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: pegylated filgrastim and filgrastim
Drug: filgrastim and pegylated filgrastim
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Multicenter, Randomized, Cross-over Phase 3 Comparing Preventive Pegylated Filgrastim and Filgrastim in Cancer Patients Receiving Myelosuppressive Chemotherapy

Resource links provided by NLM:


Further study details as provided by Chinese Academy of Medical Sciences:

Primary Outcome Measures:
  • Protective rate of grade 4 neutropenia [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    the rate of ANC keeps above 0.5 × 109 /l through the whole cycle


Secondary Outcome Measures:
  • rate of grade 3/4 neutropenia [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    the rate of ANC lower than 1.0 × 109 /l

  • time to neutrophil recovery [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    the time from chemotherapy administration until the patient's ANC increased to 2.0 × 109/l after the expected nadir

  • incidence of antibiotic administration [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    rate of using antibiotic in a cycle

  • ANC profile [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    the dynamic change of ANC number

  • incidence and severity adverse events [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    unexpected and untoward events

  • incidence and severity of side effects [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    expected and untoward events caused by study drug or control drug

  • changes in clinical laboratory values [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    changes in clinical laboratory values

  • incidence of febrile neutropenia [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    rate of ANC<0.5×109/L and auxiliary temperature>38.0℃


Enrollment: 337
Study Start Date: January 2006
Study Completion Date: December 2008
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AOB,pegylated filgrastim to filgrastim
patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5 ug/kg/d in cycle 2
Drug: pegylated filgrastim and filgrastim
patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5 ug/kg/d in cycle 2
Active Comparator: BOA,filgrastim to pegylated filgrastim
patients received filgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2
Drug: filgrastim and pegylated filgrastim
patients received filgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01285219

Sponsors and Collaborators
Chinese Academy of Medical Sciences
Fujian Cancer Hospital
Beijing Chest Hospital
Hospital affiliated to Academy of Military Medical Sciences
Tianjin Medical University Cancer
Fudan University
China Medical University, China
Hunan Cancer Hospital
West China Hospital
Second Affiliated Hospital of Dalian Medical University
Peking University Third Hospital
Tianjin People's Hospital
Qilu Hospital
Zhejiang Cancer Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Investigators
Principal Investigator: Yuankai Shi, M.D. Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Yuankai Shi, Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China
ClinicalTrials.gov Identifier: NCT01285219     History of Changes
Other Study ID Numbers: PEG3, 2002SL0047
Study First Received: January 24, 2011
Last Updated: January 26, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Chinese Academy of Medical Sciences:
Granulocyte colony-stimulating factor , recombinant
Polyethylene glycols
Neutropenia
Drug therapy, combination

Additional relevant MeSH terms:
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014