An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+
- Conditions
- Cervical Intraepithelial Neoplasia
- Interventions
- Biological: ADXS11-001 (Lm-LLO-E7)Drug: Placebo Control
- Registration Number
- NCT01116245
- Lead Sponsor
- Advaxis, Inc.
- Brief Summary
Cervical cancer is associated with Human Papilloma Virus. About 57% of cervical cancer is the result of infection by Human Papilloma Virus strain 16 (HPV-16). HPV is a very common virus that can affect the cells of the cervix. E7 is a substance that is made by the HPV virus which causes cervical cancer. The purpose of the study is to test the safety, tolerability (how the drug makes you feel), immunology (effects on the immune system) and efficacy (disease curing effects) of a vaccine called Lovaxin C against E7. The vaccine is designed to cause the immune system to react against the E7 substance in a manner that is intended to reverse the changes to the cervix and prevent cervical cancer from occurring.
- Detailed Description
Worldwide, many women carry HPV and cervical cancer is the leading cancer killer of women under the age of 50. Although its consequences are considerably less severe in the US, it leads to considerable morbidity. Many published clinical trials describe the immunotherapeutic treatment of early stage, pre-invasive, cervical cancer. It is widely recognized that immunotherapies are most effective in early stage disease because the immune system is least debilitated and disease burden is lowest. Invasive cervical cancer is preceded by a long, slowly progressive, pre-invasive phase termed Cervical Intraepithelial Neoplasia (CIN), which allows for this therapeutic approach. An ideal therapy would result in the remission of CIN 2/3 without damage to cervical tissue. A National Institute of Cancer panel charged with achieving consensus on this issue concluded that a non-surgical medical treatment for this indication would be valuable
The primary objectives of this trial are to test three doses of Lovaxin C to determine if vaccination with Lovaxin C in women with CIN 2/3 for whom surgery is indicated can safely reverse the disease compared to placebo treated control patients.
An earlier Phase 1/2 trial of Lovaxin-C in late stage metastatic cervical cancer used a regimen of two doses given with a 28-day interval. That regimen was shown to be safe and to generate reduction in tumor burdens in some patients. In this trial we will treat earlier stage disease in healthier patients with better immune systems, will use the same and lower doses as given before, but add an additional dosing to the regimen by administering the lowest dose that we assessed previously and by adding a third vaccination to the prior regimen. Unlike the phase 1 trial in which 2 doses were given with a 3 week separation, dosing in the proposed trial will be separated by 4-week intervals.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 81
- Histologically confirmed CIN 2/3 that requires surgical intervention
- Previous history of listeriosis
- Steroid use
- Antibiotic use
- Negative anergy panel
- HIV positive
- Pregnant or actively trying during the treatment period
- Intercurrent disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low Dose ADXS11-001 (Lm-LLO-E7) 5x10\^7 cfu x 3 intravenous infusions at 28 day intervals. All infusions will be preceded by prophylactic NSAID and antihistamine, and followed 3d later with antibiotic. Placebo Placebo Control normal saline x 3 intravenous infusions at 28 day intervals. All infusions will be preceded by prophylactic NSAID and antihistamine, and followed 3d later with antibiotic. High Dose ADXS11-001 (Lm-LLO-E7) 1x10\^9 cfu x 3 intravenous infusions at 28 day intervals. All infusions will be preceded by prophylactic NSAID and antihistamine, and followed 3d later with antibiotic. Middle Dose ADXS11-001 (Lm-LLO-E7) 3.3x10\^8 cfu x 3 intravenous infusions at 28 day intervals. All infusions will be preceded by prophylactic NSAID and antihistamine, and followed 3d later with antibiotic.
- Primary Outcome Measures
Name Time Method The primary end point will be a histologic determination of whether CIN 2/3 present at entry had regressed. 11 months
- Secondary Outcome Measures
Name Time Method Secondary efficacy endpoints include whether HPV DNA was reduced or eliminated and a comparison of their excised cervical tissue controls to assess the extent of disease in treated vs. untreated patients. 11 months
Trial Locations
- Locations (15)
Center for Women
🇺🇸Chicago, Illinois, United States
Indiana University Dept. of OB/GYN Oncology
🇺🇸Indianapolis, Indiana, United States
InVisions Consultants, LLC- c/o Institute for Women's Health
🇺🇸San Antonio, Texas, United States
Wasatch Clinical Research
🇺🇸Salt Lake City, Utah, United States
Altus Research
🇺🇸Lake Worth, Florida, United States
Visions Clinical Research
🇺🇸Boynton Beach, Florida, United States
New Horizons Women's Care, LLC
🇺🇸Chandler, Arizona, United States
Precision Trials
🇺🇸Phoenix, Arizona, United States
Visions Clinical Research - Tucson
🇺🇸Tucson, Arizona, United States
Grossmont Center for Clinical Research
🇺🇸La Mesa, California, United States
InVisions Consultants, LLC
🇺🇸San Antonio, Texas, United States
Arizona OB/GYN Affiliates, PC
🇺🇸Phoenix, Arizona, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
New York Downtown Hospital
🇺🇸New York, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States