Cervical Intraepithelial NeoplasiaPhase 2ADXS11-001NCT01116245
An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+
A Phase 2 study testing ADXS11-001 (Lm-LLO-E7) in people with Cervical Intraepithelial Neoplasia, run by Advaxis, Inc. at 15 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia
- What is being tested?
- ADXS11-001 (Lm-LLO-E7)
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 15 sitesUnited States
- Study dates
- Apr 2010to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Histologically confirmed CIN 2/3 that requires surgical intervention
Who cannot join
- Previous history of listeriosis
- Steroid use
- Antibiotic use
- Negative anergy panel
- HIV positive
- Pregnant or actively trying during the treatment period
- Intercurrent disease
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Visions Clinical Research
Boynton Beach, Florida, 33472
New Horizons Women's Care, LLC
Chandler, Arizona, 85224
Center for Women
Chicago, Illinois, 60612
Indiana University Dept. of OB/GYN Oncology
Indianapolis, Indiana, 46202
Grossmont Center for Clinical Research
La Mesa, California, 91942
Altus Research
Lake Worth, Florida, 33461
New York Downtown Hospital
New York, New York, 10038
Temple University
Philadelphia, Pennsylvania, 19140
Arizona OB/GYN Affiliates, PC
Phoenix, Arizona, 85016
Precision Trials
Phoenix, Arizona, 85032
Wasatch Clinical Research
Salt Lake City, Utah, 84107
InVisions Consultants, LLC- c/o Institute for Women's Health
San Antonio, Texas, 78212
InVisions Consultants, LLC
San Antonio, Texas, 78217
Montefiore Medical Center
The Bronx, New York, 10461
Visions Clinical Research - Tucson
Tucson, Arizona, 85712
About this study
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
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.
Read the 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.
- Conditions
- Cervical Intraepithelial Neoplasia
- Being tested
- ADXS11-001 (Lm-LLO-E7), Placebo Control
- Keywords
- Cervical Intraepithelial Neoplasia Stage 2/3
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADXS11-001 (Lm-LLO-E7)Biological
ADXS11-001 at one of three dose levels given as 3 vaccinations separated by 4 weeks with an oral antibiotic regimen subsequent to dosing.
Placebo ControlDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | 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. Receives: Biological: ADXS11-001 (Lm-LLO-E7) |
| Middle Dose | Experimental | 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. Receives: Biological: ADXS11-001 (Lm-LLO-E7) |
| High Dose | Experimental | 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. Receives: Biological: ADXS11-001 (Lm-LLO-E7) |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end point will be a histologic determination of whether CIN 2/3 present at entry had regressed.
Measured: 11 months
Secondary outcomes (1)
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.
Measured: 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2013
- Study completionApr 2016
Why it stopped: Study stopped due to lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advaxis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116245
- Sponsor's protocol ID
- Lm-LLO-E7-07
- Acronym
- ADXS11-001
- Status last verified
- Jul 2016
- First submitted
- 20 Apr 2010
- Last updated
- 27 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01116245
- Acronym / sponsor ID
- ADXS11-001 / Lm-LLO-E7-07
- Conditions
- Cervical Intraepithelial Neoplasia
- Keywords
- Cervical Intraepithelial Neoplasia Stage 2/3
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped due to lack of enrollment
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Advaxis, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 4 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Biological: 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. |
| Middle Dose | Experimental | Biological: 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. |
| High Dose | Experimental | Biological: 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. |
| Placebo | Placebo comparator | Drug: Placebo Controlnormal 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Histologically confirmed CIN 2/3 that requires surgical intervention
Key exclusion criteria (7 listed)
- Previous history of listeriosis
- Steroid use
- Antibiotic use
- Negative anergy panel
- HIV positive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | High Dose, Low Dose, Middle Dose |
| Placebo Control3 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. | Drug | Placebo |
Primary outcome
The primary end point will be a histologic determination of whether CIN 2/3 present at entry had regressed.
Time frame: 11 months
1 secondary outcome
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.
Time frame: 11 months
Results and safety
The study was stopped early (reason given: Study stopped due to lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ADXS11-001 (Lm-LLO-E7) in people with Cervical Intraepithelial Neoplasia, run by Advaxis, Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study stopped due to lack of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary end point will be a histologic determination of whether CIN 2/3 present at entry had regressed. (time frame: 11 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2016.