An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+

Cervical Intraepithelial Neoplasia Clinical Trial

— ADXS11-001  

Official title:

A Randomized, Single Blind, Placebo Controlled Phase 2 Study to Assess the Safety of ADXS11-001 for the Treatment of Cervical Intraepithelial Neoplasia Grade 2/3

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01116245
• Other study ID #: Lm-LLO-E7-07
• Status: Terminated
• Phase: Phase 2
• First received: April 20, 2010
• Last updated: July 26, 2016
• Start date: April 2010
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Advaxis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 81
• Est. completion date: April 2016
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed CIN 2/3 that requires surgical intervention

Exclusion Criteria:

• 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Neoplasms

Intervention

Biological:
• ADXS11-001 (Lm-LLO-E7)
ADXS11-001 at one of three dose levels given as 3 vaccinations separated by 4 weeks with an oral antibiotic regimen subsequent to dosing.

Drug:
• Placebo Control
3 intravenous infusions of normal saline at 28 day intervals. All infusions will be preceded by prophylactic NSAID and antihistamine, and followed 3d later with antibiotic.

Locations

Country	Name	City	State
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	New Horizons Women's Care, LLC	Chandler	Arizona
United States	Center for Women	Chicago	Illinois
United States	Indiana University Dept. of OB/GYN Oncology	Indianapolis	Indiana
United States	Grossmont Center for Clinical Research	La Mesa	California
United States	Altus Research	Lake Worth	Florida
United States	New York Downtown Hospital	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Arizona OB/GYN Affiliates, PC	Phoenix	Arizona
United States	Precision Trials	Phoenix	Arizona
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	InVisions Consultants, LLC	San Antonio	Texas
United States	InVisions Consultants, LLC- c/o Institute for Women's Health	San Antonio	Texas
United States	Visions Clinical Research - Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Advaxis, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point will be a histologic determination of whether CIN 2/3 present at entry had regressed.		11 months	Yes
Secondary	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	No