Study of ADXS11-001 in Participants With High Risk Locally Advanced Cervical Cancer (AIM2CERV)

February 15, 2023 updated by: Advaxis, Inc.

Phase 3 Study of ADXS11-001 Administered Following Chemoradiation as Adjuvant Treatment for High Risk Locally Advanced Cervical Cancer: AIM2CERV

Locally advanced cervical cancer at higher risk for recurrence (HRLACC) following concurrent chemotherapy and radiation therapy. This is a group of participants with a significant unmet need. The estimated probability of disease recurrence or death within 4 years of diagnosis is 50% and the prognosis is very grave for those who experience a recurrence.

The purpose of the study was to compare the disease free survival (DFS) of ADXS11-001 to placebo administered following cisplatin-based combination chemotherapy and radiation (CCRT) with curative intent in participants with HRLACC.

Study Overview

Status

Terminated

Intervention / Treatment

Detailed Description

This was a double-blind, placebo-controlled randomized study of ADXS11-001 administered in the adjuvant setting after completion of CCRT in participants with HRLACC, or death. All eligible participants had received CCRT administered with curative intent according to institutional/national guidelines as well as meeting the minimum standards defined in the protocol. Participants initiated the Screening period within 10 weeks after the completion of CCRT. Baseline radiographic assessments and clinical laboratory assessments were completed no longer than 28 days prior to and 3 days prior to the first study treatment infusion, respectively. Eligible participants were randomized 1:2 to receive either placebo or ADXS11-001. Participants received 1 infusion of study treatment administered every 3 weeks for 3 doses for the first 3 months. Thereafter, participants received study treatment every 8 weeks for a total of 5 doses or until disease recurrence. Participants received a 7-day course of an oral antibiotic or placebo starting 72 hours following the completion of study treatment administration.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • La Rioja, Argentina, F5300 COE
        • Site
    • RJ
      • Rio De Janeiro, RJ, Brazil, 20220-410
        • Site
    • RN
      • Natal, RN, Brazil, 59075-740
        • Site
    • Alberta
      • Calgary, Alberta, Canada, T2N4N2
        • Site
    • Quebec
      • Montréal, Quebec, Canada, H2X0A9
        • Site
      • Sherbrooke, Quebec, Canada, J1H5N4
        • Site
    • Araucania
      • Temuco, Araucania, Chile, 4810469
        • Site
    • Region Metropolitana
      • Santiago de Chile, Region Metropolitana, Chile, 7500836
        • Site
      • Seongnam, Korea, Republic of, 13496
        • Site
      • Seoul, Korea, Republic of, 1812
        • Site
      • Seoul, Korea, Republic of, 3080
        • Site
      • Seoul, Korea, Republic of, 3722
        • Site
      • Seoul, Korea, Republic of, 5505
        • Site
      • Seoul, Korea, Republic of, 6273
        • Site
      • Seoul, Korea, Republic of, 6351
        • Site
      • Yangsan, Korea, Republic of, 50612
        • Site
      • Kuala Lumpur, Malaysia, 59100
        • Site
      • Pulau Pinang, Malaysia, 13200
        • Site
    • Kelantan
      • Kota Bharu, Kelantan, Malaysia, 15586
        • Site
      • Kota Bharu, Kelantan, Malaysia, 16150
        • Site
    • Selangor
      • Ampang, Selangor, Malaysia, 68000
        • Site
      • Chihuahua, Mexico, 31217
        • Site
    • D.f.
      • Mexico City, D.f., Mexico, CP 06760
        • Site
      • Białystok, Poland, 15-027
        • Site
      • Lublin, Poland, 20-090
        • Site
      • Arkhangel'sk, Russian Federation, 163045
        • Site
      • Moscow, Russian Federation, 115478
        • Site
      • Nal'chik, Russian Federation, 360000
        • Site
      • Nizhny Novgorod, Russian Federation, 603006
        • Site
      • Obninsk, Russian Federation, 249036
        • Site
      • Orenburg, Russian Federation, 460021
        • Site
      • Pyatigorsk, Russian Federation, 357502
        • Site
      • Rostov-on-Don, Russian Federation
        • Site
      • Saint Petersburg, Russian Federation, 197758
        • Site
      • Saint Petersburg, Russian Federation, 198255
        • Site
      • Sochi, Russian Federation, 354057
        • Site
      • Ufa, Russian Federation, 450054
        • Site
      • Volgograd, Russian Federation, 400131
        • Site
    • Krasnodar Region
      • Krasnodar, Krasnodar Region, Russian Federation, 350040
        • Site
      • Belgrade, Serbia, 11000
        • Site
      • Belgrade, Serbia, 11080
        • Site
      • Kragujevac, Serbia, 34000
        • Site
      • Sremska Kamenica, Serbia, 21204
        • Site
      • Barcelona, Spain, 8035
        • Site
      • Barcelona, Spain, 8041
        • Site
      • Barcelona, Spain, 8908
        • Site
      • Córdoba, Spain, 14004
        • Site
      • El Palmar, Spain, 46010
        • Site
      • Elche, Spain, 3203
        • Site
      • Girona, Spain, 17007
        • Site
      • Madrid, Spain, 28046
        • Site
      • Madrid, Spain, 28050
        • Site
      • Málaga, Spain, 29010
        • Site
      • Palma De Mallorca, Spain, 7120
        • Site
      • Palma De Mallorca, Spain, 7198
        • Site
      • Sabadell, Spain, 8208
        • Site
      • Seville, Spain, 41013
        • Site
      • Valencia, Spain, 46009
        • Site
      • Valencia, Spain, 46010
        • Site
      • Zaragoza, Spain, 50009
        • Site
      • Taichung, Taiwan, 40705
        • Site
      • Tainan, Taiwan, 704
        • Site
      • Taipei, Taiwan, 10002
        • Site
      • Taipei, Taiwan, 10630
        • Site
      • Taipei, Taiwan, 11259
        • Site
      • Taoyuan, Taiwan, 3331
        • Site
      • Chernivtsi, Ukraine, 58013
        • Site
      • Dnepropetrovsk, Ukraine, 49102
        • Site
      • Ivano-Frankivs'k, Ukraine, 76018
        • Site
      • Kharkiv, Ukraine, 61070
        • Site
      • Khmelnytskyi, Ukraine, 29009
        • Site
      • Luts'k, Ukraine, 43018
        • Site
      • Poltava, Ukraine, 36011
        • Site
      • Ternopil', Ukraine, 46000
        • Site
      • Vinnytsia, Ukraine, 21029
        • Site
      • Zaporizhzhya, Ukraine
        • Site
    • Alabama
      • Mobile, Alabama, United States
    • Arizona
      • Phoenix, Arizona, United States
      • Phoenix, Arizona, United States
        • Site
    • California
      • Duarte, California, United States
      • Long Beach, California, United States
      • Orange, California, United States
      • Orange, California, United States, 92868
        • Site
      • San Francisco, California, United States
        • Site
    • Florida
      • Miami, Florida, United States
        • Site
      • Tallahassee, Florida, United States
        • Site
      • Tampa, Florida, United States
    • Georgia
      • Augusta, Georgia, United States
    • Illinois
      • Maywood, Illinois, United States
      • Park Ridge, Illinois, United States
        • Site
    • Indiana
      • Indianapolis, Indiana, United States
      • Indianapolis, Indiana, United States
        • Site
    • Iowa
      • Iowa City, Iowa, United States
    • Maine
      • Scarborough, Maine, United States
    • Maryland
      • Baltimore, Maryland, United States
        • Site
    • Michigan
      • Detroit, Michigan, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • Nebraska
      • Omaha, Nebraska, United States
        • Site
    • Nevada
      • Las Vegas, Nevada, United States
        • Site
    • New Jersey
      • Hackensack, New Jersey, United States
        • Site
      • Newark, New Jersey, United States, 07103
        • Site
    • New York
      • Albany, New York, United States, 12208
      • Brooklyn, New York, United States
        • Site
    • North Carolina
      • Charlotte, North Carolina, United States
      • Winston-Salem, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Site
      • Hilliard, Ohio, United States
        • Site
      • Kettering, Ohio, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • South Carolina
      • Greenville, South Carolina, United States
    • Tennessee
      • Chattanooga, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
        • Site
      • Galveston, Texas, United States
        • Site
      • Houston, Texas, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Participants must have a biopsy confirmed diagnosis of squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix. Histologic confirmation of the original primary tumor is required.
  • Participants with HRLACC.
  • Participants included those with stage IB2, IIA2, IIB with pelvic lymph node metastases; all FIGO Stage IIIA, IIIB, IVA or any FIGO Stage (except stage IVB) with para-aortic lymph node metastases as defined by the FIGO 2014 staging criteria for carcinoma of the cervix uteri.
  • Participants must have received definitive therapy with curative intent, which consist of at least 4 weeks of treatment with cisplatin and a minimum of 40Gy external beam radiation therapy (EBRT).
  • Have performance status of 0 or 1 on the gynaecologic Oncology Group (GOG) performance scale
  • Demonstrate adequate organ function

Exclusion Criteria:

  • Has not achieved disease-free status after completion of CCRT administered with curative intent.
  • Has International Federation of Gynecology and Obstetrics (FIGO) Stage IVB
  • Has histologies other than squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix.
  • Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)).
  • Has a contraindication (sensitivity or allergy) to trimethoprim/sulfamethoxazole and ampicillin.
  • Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who have had a partial/subtotal hysterectomy are eligible to participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Participants with locally advanced cervical cancer at higher risk for recurrence (HRLACC) received ADXS11-001 matching placebo by intravenous infusion for approximately 60 minutes every 3 weeks for 3 doses (Weeks 1, 4 and 7) and thereafter, every 8 weeks for 5 doses (Weeks 15, 23, 31, 39, and 47) during treatment phase or until disease recurrence. Participants received a 7-day course placebo matching to either trimethoprim/sulfamethoxazole or ampicillin starting 72 hours post treatment in prime and maintenance phase.
Experimental: ADXS11-001
Participants with HRLACC received ADXS11-001 at a dose of 1x10^9 colony forming units (CFU) by intravenous infusion for approximately 60 minutes every 3 weeks for 3 doses (Weeks 1, 4 and 7) and thereafter, every 8 weeks for 5 doses (Weeks 15, 23, 31, 39, and 47) during treatment phase or until disease recurrence. Participants received a 7-day course of either trimethoprim/sulfamethoxazole or ampicillin starting 72 hours post treatment in prime and maintenance phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: From the time of randomization to recurrence or death (Maximum duration: 44.7 months)
DFS was defined as the time from randomization until death or recurrence. The date of recurrence was defined as the date of the first time point when recurrence of disease was determined. The determination of recurrence should occur by definitive pathologic tissue confirmation (e.g., biopsy/fine needle aspirate). However, in those cases where it was not medically feasible to obtain a tissue sample then radiographic evidence, when confirmed by independent radiology review, was used to determine recurrence.
From the time of randomization to recurrence or death (Maximum duration: 44.7 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events
Time Frame: From first dose of study drug until end of study (Up to 44.7 months)
Adverse event (AE): any untoward medical occurrence in a participant administered a study treatment & which did not necessarily have to have a causal relationship with the study treatment. An AE is, any unfavorable & unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of study treatment. AE with onset dates on or after the first dose of study treatment were considered treatment emergent.
From first dose of study drug until end of study (Up to 44.7 months)
Overall Survival (OS)
Time Frame: From the date of randomization until death due to any cause (Maximum duration: 44.7 months)
Overall survival was defined as the time from the date of randomization until death due to any cause.
From the date of randomization until death due to any cause (Maximum duration: 44.7 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Thomas J Herzog, MD, University of Cincinnati
  • Principal Investigator: Brian Slomovitz, MD, Sylvester Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2015

Primary Completion (Actual)

July 31, 2019

Study Completion (Actual)

July 31, 2019

Study Registration Dates

First Submitted

July 28, 2016

First Submitted That Met QC Criteria

July 29, 2016

First Posted (Estimate)

August 3, 2016

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

February 15, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • ADXS001-02
  • 2015-004844-20 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on High Risk Cervical Cancer

Clinical Trials on Placebo

3
Subscribe