Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of YPEG-Filgrastim in Chemotherapy Patients (Filgrastim)

A Randomized, Open-label, Single-dose, Dose-escalation, Self-controlled Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of YPEG-Filgrastim in Cancer Patients Receiving Chemotherapy

This study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics of a single-dose of YPEG-Filgrastim in cancer patients receiving chemotherapy, and will establish dose-response relationships between YPEG-Filgrastim and Filgrastim(rhG-CSF, TOPNEUTER).

Study Overview

• Status: Completed
• Conditions: Chemotherapy Patients
• Intervention / Treatment: Drug: YPEG-Filgrastim; Drug: YPEG-Filgrastim; Drug: YPEG-Filgrastim; Drug: YPEG-Filgrastim; Drug: YPEG-Filgrastim

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18～70yrs
• Signed informed consent
• Confirmed malignant tumor patients by histopathological or cytological diagnosis, suitable for chemotherapy with carboplatin combined with taxol or cyclophosphamide combined with pharmorubicin
• Karnofsky score ≥70
• Life expectancy >3 months
• WBC≥3,500 per cubic milliliter, ANC≥1,500 per cubic milliliter, PLT≥100,000 per cubic milliliter
• Normal coagulation function, no evidences of hemorrhage
• Normal liver, heart, kidney function

Exclusion Criteria:

• Pregnant or lactating females
• Proven active infectious diseases (e.g. viral hepatitis, TB)
• Not adequately controlled infections
• Known hypersensitivity to filgrastim or any other components of the study drug
• Unstable or uncontrolled cardiac disease or hypertension
• Currently participated in any other clinical trials
• Patients with previous or expected to receive systemic radiotherapy
• Evidence of metastatic disease in bone marrow, brain, et al
• Alcoholic or drug abusers
• Other conditions which in the opinion of the investigator preclude enrollment into the study

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: YPEG-Filgrastim, 10mcg/kg	Drug: YPEG-Filgrastim; s.c, single dose of 10mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 20mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 30mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 45mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir; Drug: YPEG-Filgrastim; s.c, single dose of 60mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.
EXPERIMENTAL: YPEG-Filgrastim, 20mcg/kg	Drug: YPEG-Filgrastim; s.c, single dose of 10mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 20mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 30mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 45mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir; Drug: YPEG-Filgrastim; s.c, single dose of 60mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.
EXPERIMENTAL: YPEG-Filgrastim, 30mcg/kg	Drug: YPEG-Filgrastim; s.c, single dose of 10mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 20mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 30mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 45mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir; Drug: YPEG-Filgrastim; s.c, single dose of 60mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.
EXPERIMENTAL: YPEG-Filgrastim, 45mcg/kg	Drug: YPEG-Filgrastim; s.c, single dose of 10mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 20mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 30mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 45mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir; Drug: YPEG-Filgrastim; s.c, single dose of 60mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.
EXPERIMENTAL: YPEG-Filgrastim, 60mcg/kg	Drug: YPEG-Filgrastim; s.c, single dose of 10mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 20mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 30mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.; Drug: YPEG-Filgrastim; s.c, single dose of 45mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir; Drug: YPEG-Filgrastim; s.c, single dose of 60mcg/kg of YPEG-Filgrastim at 48hr of cycle 2, followed by daily s.c either 2.5 mcg/kg or 5 mcg/kg of filgrastim(TOPNEUTER) starting from 48hr of cycle 3 until WBC≥10,000 per cubic milliliter or ANC≥5,000 per cubic milliliter in two continuous daily tests after ANC nadir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measurement of absolute neutrophil counts in the 3 cycles for pharmacodynamic study.	each cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
Measurement of serum concentration of drugs for Pharmacokinetic study.	each cycle

Collaborators and Investigators

• Sponsor: Xiamen Amoytop Biotech Co., Ltd.
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Shi Yuankai, Ph.D, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: November 5, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (ESTIMATE): November 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 4, 2013
• Last Update Submitted That Met QC Criteria: January 31, 2013
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: chemotherapy; carboplatin; cyclophosphamide; taxol; cancer patient; pharmorubicin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: TB1004CSF