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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00497809
• Other study ID #: AVI-014-P02
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2007
• Last updated: May 2, 2011
• Start date: August 2007
• Est. completion date: July 2009

Study information

• Verified date: May 2011
• Source: AviGenics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRomania: National Medicines AgencyIndia: Institutional Review BoardIndia: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: July 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neutropenia

Intervention

Drug:
• AVI-014 versus Filgrastim
3 different dose arms of AVI-014 versus Filgrastim for up to 14 days daily

Locations

Country	Name	City	State
India	Apollo Specialty Hospital, Padma Complex	320 Mount Road	Chennai
India	Ruby Hall Clinic	40 Sasoon Road	Pune
India	Amrita Institute of Medical Sciences	Amrita Lane Elamakkara	Cochin
India	Kasturba Medical College Hospital	Attavar	Mangalore
India	Kidwai Memorial Institute of Oncology, Dr. M.H. Marigowda Road	Bangalore	Karnataka
India	Indraprastha Apollo Hospital	Delhi Mathura road, Sarita vihar	New Delhi
India	Tata Memorial Hospital,	Dr. E Borges Road, Parel	Mumbai
India	Mohan Dai Oswal Cancer Treatment & Research Foundation	G.T. Road, Sherpur Bye Pass	Ludhiana
India	Jawaharlal Nehru Cancer Hospital and Research Centre	Idgah Hills	Bhopal
India	Apollo Hospitals Educational and Research Foundation	Jubilee hills	Hyderabad
India	Meenakshi Mission Hospital and Research Centre	Lake Area, Melur Road	Madurai,
India	IRCH, AIIMS, Ansari Nagar,	New Delhi
India	Regional Cancer Centre, IGIMS	Sheikhpura	Patna
India	Dayanand Medical College and Hospital	Tagore Nagar, Civil Lines	Ludhiana
India	Dharamshila Cancer Center, Dharamshila Marg	Vasundhara Enclave	New Delhi
India	Dharamshila Hospital and research Centre	Vasundhara Enclave	Delhi
India	King George Hospital	Vizag	Vishakhapattanam
United States	Cancer Outreach Associates PC	Abingdon	Virginia
United States	Cancer Care Institute of Carolina	Aiken	South Carolina
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Gabrail Cancer Center	Canton	Ohio
United States	Southern Illinois Hematology/Oncology	Centralia	Illinois
United States	Cancer Specialists of South Texas	Corpus Christi	Texas
United States	Physicians Research Alliance LLC.	Debary	Florida
United States	California Cancer Center	Greenbrae	California
United States	Ghassan Al-Jazayrly, MD, Inc.	Los Angeles	California
United States	Signal Point Clinical Research Center, LLC	Middletown	Ohio
United States	University of Oklahoma Health Sciences Ctr	Oklaoma City	Oklahoma
United States	Desert Hematology Oncology Medical Group	Rancho Mirage	California
United States	Brian LeBerthon, MD, A Medical Corporation	West Covina	California
United States	Infosphere Clinical Research	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
AviGenics

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy endpoint is duration of grade 4 neutropenia (DSN), defined as ANC <0.5 x 109/L during chemotherapy cycle 1.		First cycle of GCSF	No
Secondary	• 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)		Cycle 1	No