Randomized, Double Blind Trial of the Quadrivalent HPV Vaccine to Improve Responses to LEEP Treatment of Cervical HSIL

June 11, 2020 updated by: Cynthia S Firnhaber, University of Witwatersrand, South Africa

A Randomized, Placebo-controlled Trial of Pre-treatment HPV Vaccination on Outcomes to LEEP Treatment of Cervical High Grade Squamous Intraepithelial Lesions in HIV-infected Women.

Cervical cancer occurs commonly in HIV-infected women in South Africa. These women have poor response to treatment of cervical cancer precursors. This study will test whether giving the quadrivalent vaccine to women prior to surgical treatment of the cervical cancer precursor will improve outcomes. We hypothesize that pre-treatment HPV vaccine will result in a reduced occurrence or cervical cancer precursors in follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single-center, randomized, double-blinded, placebo-controlled, phase II trial of the quadrivalent human papillomavirus vaccine (qHPV) in HIV-infected women to prevent occurrence of cervical HSIL after LEEP/LLETZ. Participants will undergo colposcopy with directed biopsies, cervical cytology, and stored HPV testing prior to vaccination. Participants will be randomized to the quadrivalent vaccine or saline placebo to be given at entry, week 4, and week 26. Women will have LEEP treatment at week 4. Participants will be seen in follow-up for cervical cytology, colposcopy with directed biopsies at weeks 26 and 52, and stored HPV specimens. Treatment assignment will be unblinded after study follow-up is completed for the last study participant. Women aged 45 or less randomized to placebo will be offered open label HPV vaccine after the study is concluded..

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
180

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. HIV infection
  2. Women aged ≥ 18 years.
  3. Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3)
  4. For participants of reproductive potential, negative serum or urine pregnancy test
  5. All study participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) during study participation (from the time of study entry until week 52).

Exclusion Criteria:

  1. History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer
  2. Prior hysterectomy
  3. Cervical cryotherapy or LEEP/LEETZ within one year of entry.
  4. Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer
  5. Prior receipt of one or more doses of an HPV vaccine.
  6. Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry.
  7. Known allergy/sensitivity or any hypersensitivity to yeast or any of the components of the study product or its formulation (see section 5.2 for a list of components).
  8. Hemophilia or other bleeding diatheses.
  9. Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, other than inhaled corticosteroids or prednisone ≤ 10 mg (or equivalent) , investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.
  10. Breastfeeding
  11. Less than 3 months post-partum

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Human Papillomavirus vaccine
Participants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26.
Biological: Human Papillomavirus vaccine
The participants receive the qHPV vaccine at entry, week 4 and week 26
Other Names:
  • qHPV vaccine
PLACEBO_COMPARATOR: Saline placebo
The participants receive saline placebo at entry, week 4 and week 26.
Biological: Human Papillomavirus vaccine
The participants receive the qHPV vaccine at entry, week 4 and week 26
Other Names:
  • qHPV vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cervical HSIL
Time Frame: up to 52 weeks
For this trial, the primary endpoint is high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells suggestive of HSIL found on cervical cytology, or HSIL found on cervical biopsy specimens at either the week 26 or week 52 visit.
up to 52 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cervical Cytology
Time Frame: Week 26
Cervical cytology abnormalities according to the Bethesda scale. The Bethesda scale classifies cytologic abnormalities. We have dichotomized the outcomes into high grade squamous intraepithelial lesions (HSIL)/atypical squamous cells suggestive of HSIL, or no evidence of intraepithelial lesions or malignancy (NILM)/atypical squamous cells of unknown significance (ASC-US)/low grade squamous intraepithelial lesions (LSIL). We report the number of women in each category.
Week 26

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Witwatersrand, South Africa

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Timothy J Wilkin, M.D. MPH, Weill Medical College of Cornell University
  • Study Chair: Cynthia Firnhaber, M.D., University or Witswatersrand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 2, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 20, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 23, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • QHPV-RTC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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