Safety and Efficacy Study of GCSF Therapy to Treat Patients at High Risk for Chemotherapy Induced Severe Neutropenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00497809
Recruitment Status : Completed
First Posted : July 9, 2007
Last Update Posted : May 3, 2011
Information provided by:

Brief Summary:
The overall purpose of this study is to assess the dose response, efficacy, and safety of three different dose levels of AVI 014 (granulocyte colony-stimulating factor [G-CSF]) in breast cancer patients at high (>20%) risk for chemotherapy-induced severe neutropenia.

Condition or disease Intervention/treatment Phase
Breast Cancer Neutropenia Drug: AVI-014 versus Filgrastim Phase 2

Detailed Description:

Filgrastim is a recombinant human G-CSF (rhG-CSF) developed in the mid 1980s, and was approved by the United States (US) Food and Drug Administration (FDA) for use in chemotherapy induced neutropenia in 1991 under the trade name Neupogen®. Filgrastim was first approved in the EU in Germany in 2001 under the same trade name. Filgrastim is a non glycosylated protein, produced in E. coli bacteria transfected with rhG-CSF copy deoxyribonucleic acid (cDNA). Filgrastim differs from native human G CSF only in the addition of an N terminal methionine required for expression in a bacterial host. In 2002, a pegylated filgrastim with extended duration of action relative to the naked filgrastim was approved by the FDA and the EU Commission under the trade name Neulasta.

AviGenics has generated transgenic hens carrying rhG CSF cDNA, which express a glycosylated form of rhG-CSF protein in their egg white. The purified rhG-CSF is biologically active, as assessed by its in vitro binding and cell proliferation activities, and has been fully characterized by AviGenics. AviGenics intends to develop this product to treat chemotherapy-induced neutropenia.

The overall goal of this study is to assess dose response, efficacy, and safety of three different dose levels of AVI-014 (G-CSF) in breast cancer patients at high (>20%) risk for chemotherapy induced severe neutropenia.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 189 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Dose Finding, Prospective, Multi Center, Randomized, Parallel Group Study to Assess the Efficacy and Safety of Three Different Dose Levels of AVI 014 (G-CSF) Compared With a Standard Dose of Neupogen® in Breast Cancer Patients at High (>20%) Risk for Chemotherapy Induced Severe Neutropenia
Study Start Date : August 2007
Actual Primary Completion Date : July 2008
Actual Study Completion Date : July 2009

Arm Intervention/treatment
Experimental: 1
AVI-014 2.5mcg/kg
Drug: AVI-014 versus Filgrastim
3 different dose arms of AVI-014 versus Filgrastim for up to 14 days daily
Experimental: 2
AVI-014 5.0 mcg/kg
Drug: AVI-014 versus Filgrastim
3 different dose arms of AVI-014 versus Filgrastim for up to 14 days daily
Experimental: 3
AVI014 10.0 mcg/kg
Drug: AVI-014 versus Filgrastim
3 different dose arms of AVI-014 versus Filgrastim for up to 14 days daily
Active Comparator: 4
Filgrastim 5.0 mcg/kg
Drug: AVI-014 versus Filgrastim
3 different dose arms of AVI-014 versus Filgrastim for up to 14 days daily

Primary Outcome Measures :
  1. The primary efficacy endpoint is duration of grade 4 neutropenia (DSN), defined as ANC <0.5 x 109/L during chemotherapy cycle 1. [ Time Frame: First cycle of GCSF ]

Secondary Outcome Measures :
  1. • Incidence of grade 4 neutropenia • Duration of neutropenia (defined as the number of days with ANC <0.5 x 109/L and <0.1 x 109/L) [ Time Frame: Cycle 1 ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Able to understand and voluntarily provide written informed consent before screening, following an explanation of the nature and purpose of this study.
  • Women, aged 18 years and older
  • Histologically confirmed breast cancer, undergoing one of a variety of chemotherapy regimens, or with other risk factors that could lead to a >20% risk of developing severe neutropenia. Patients receiving chemotherapy regimens with high-risk for severe neutropenia are eligible; eligibility of patients receiving intermediate-risk chemotherapy regimens must be discussed with the Medical Monitor for the presence of additional patient-specific risk factors.
  • Must be receiving first-line adjuvant or neoadjuvant therapy for localized breast cancer or first-line chemotherapy for metastatic breast cancer. It is recommended that patients with human epidermal growth factor receptor 2 (HER2/neu)-positive breast cancer should be receiving Herceptin® (trastuzumab), if approved and available for this indication.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of grade 0 to 2
  • Adequate renal (serum creatinine and blood urea nitrogen [BUN] <3 times the upper limit of normal [ULN]) and hepatic (serum bilirubin, aspartate aminotransferase [AST], and alanine aminotransferase [ALT] <3 times ULN) function.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Women who are not pregnant and do not plan to become pregnant during the study. Women of childbearing potential must have a negative serum pregnancy test result within seven days before the first dose of study drug and must be using adequate non hormonal barrier contraception before entering the study and throughout the study. Non childbearing potential is defined as post-menopausal for at least one year, surgically sterile, or having had a hysterectomy before study start.

Exclusion Criteria:

  • Pregnant or lactating women.
  • History or clinical evidence of a serious medical illness, including renal, hepatic, respiratory, cardiovascular, endocrine, neurologic, psychiatric, or hematologic disease, which in the opinion of the investigator will interfere with study participation.
  • Metastatic brain or meningeal tumors.
  • Ascites or pleural effusions.
  • Any active infection requiring systemic antimicrobial therapy.
  • Known to be positive for human immunodeficiency virus (HIV, anti-HIV+), hepatitis B antigen (HBAg[+]), or hepatitis C antibody (HCVAb[+]).
  • Known or suspected hypersensitivity to the study drug or its components, such as avian products, including influenza vaccine, or to E. coli-derived proteins.
  • Currently receiving radiation therapy for treatment of a malignant condition, or have completed radiation therapy within 14 days before study entry. Radiation therapy for oncologic emergency is allowed.
  • Participated in another therapeutic clinical study (i.e., not an epidemiological study or genomic screening study) during the past 30 days, or are likely to simultaneously participate in another therapeutic clinical study.
  • History of, or known current problems with, substance abuse, or any medical, psychological, and/or social condition that may interfere with the patient's participation in the study, or with evaluation of the study results.
  • Any condition that could jeopardize the patient's safety and compliance, as judged by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00497809

United States, California
Pacific Cancer Medical Center
Anaheim, California, United States, 92801
California Cancer Center
Greenbrae, California, United States, 94904-2007
Ghassan Al-Jazayrly, MD, Inc.
Los Angeles, California, United States, 90027
Desert Hematology Oncology Medical Group
Rancho Mirage, California, United States, 92270
Brian LeBerthon, MD, A Medical Corporation
West Covina, California, United States, 91790
Infosphere Clinical Research
West Hills, California, United States, 91307
United States, Florida
Physicians Research Alliance LLC.
Debary, Florida, United States, 32713
United States, Illinois
Southern Illinois Hematology/Oncology
Centralia, Illinois, United States, 62801
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44781
Signal Point Clinical Research Center, LLC
Middletown, Ohio, United States, 45042
United States, Oklahoma
University of Oklahoma Health Sciences Ctr
Oklaoma City, Oklahoma, United States, 73104
United States, South Carolina
Cancer Care Institute of Carolina
Aiken, South Carolina, United States, 29801
United States, Texas
Cancer Specialists of South Texas
Corpus Christi, Texas, United States, 78412
United States, Virginia
Cancer Outreach Associates PC
Abingdon, Virginia, United States, 24211
Jawaharlal Nehru Cancer Hospital and Research Centre
Idgah Hills, Bhopal, India, 462001
Apollo Specialty Hospital, Padma Complex
320 Mount Road, Chennai, India, 600 035
Amrita Institute of Medical Sciences
Amrita Lane Elamakkara, Cochin, India, 682026
Dharamshila Hospital and research Centre
Vasundhara Enclave, Delhi, India, 10096
Apollo Hospitals Educational and Research Foundation
Jubilee hills, Hyderabad, India, 500033
Kidwai Memorial Institute of Oncology, Dr. M.H. Marigowda Road
Bangalore, Karnataka, India, 560 029
Mohan Dai Oswal Cancer Treatment & Research Foundation
G.T. Road, Sherpur Bye Pass, Ludhiana, India, 141009
Dayanand Medical College and Hospital
Tagore Nagar, Civil Lines, Ludhiana, India, 141001
Meenakshi Mission Hospital and Research Centre
Lake Area, Melur Road, Madurai,, India, 625107
Kasturba Medical College Hospital
Attavar, Mangalore, India, 576104
Tata Memorial Hospital,
Dr. E Borges Road, Parel, Mumbai, India, 400 012
Indraprastha Apollo Hospital
Delhi Mathura road, Sarita vihar, New Delhi, India, 110076
Dharamshila Cancer Center, Dharamshila Marg
Vasundhara Enclave, New Delhi, India, 110096
Regional Cancer Centre, IGIMS
Sheikhpura, Patna, India, 800014
Ruby Hall Clinic
40 Sasoon Road, Pune, India, 411001
King George Hospital
Vizag, Vishakhapattanam, India, 110076
IRCH, AIIMS, Ansari Nagar,
New Delhi, India, 110029
Sponsors and Collaborators
Principal Investigator: Howard Ozer, MD University of Oklahoma
Principal Investigator: Robert J. Grieve, M.B,Ch.B., FRCR University Hospitals of Coventry and Warwickshire
Study Chair: Walter Kraft, MD, MS, FACP AviGenics

Responsible Party: Mark Hites, Director, Regulatory Affairs, AviGenics Identifier: NCT00497809     History of Changes
Other Study ID Numbers: AVI-014-P02
First Posted: July 9, 2007    Key Record Dates
Last Update Posted: May 3, 2011
Last Verified: May 2011

Keywords provided by AviGenics:
Breast Cancer
High risk

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Leukocyte Disorders
Hematologic Diseases
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs