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

Primary Purpose

Cervical High Grade Squamous Intraepithelial Lesion

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Human Papillomavirus vaccine

About this trial

This is an interventional treatment trial for Cervical High Grade Squamous Intraepithelial Lesion focused on measuring HSIL, CIN, HPV, HPV vaccination, gardasil, HIV, cervical dysplasia, LEEP, cervical cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

HIV infection
Women aged ≥ 18 years.
Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3)
For participants of reproductive potential, negative serum or urine pregnancy test
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:

History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer
Prior hysterectomy
Cervical cryotherapy or LEEP/LEETZ within one year of entry.
Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer
Prior receipt of one or more doses of an HPV vaccine.
Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry.
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).
Hemophilia or other bleeding diatheses.
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.
Breastfeeding
Less than 3 months post-partum

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Human Papillomavirus vaccine

Saline placebo

Arm Description

Participants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26.

The participants receive saline placebo at entry, week 4 and week 26.

Outcomes

Primary Outcome Measures

Cervical HSIL

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.

Secondary Outcome Measures

Cervical Cytology

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.

Full Information

NCT ID

NCT01928225

First Posted

August 20, 2013

Last Updated

June 11, 2020

Sponsor

University of Witwatersrand, South Africa

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01928225

Brief Title

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

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

September 2, 2014 (Actual)

Primary Completion Date

November 30, 2017 (Actual)

Study Completion Date

March 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Witwatersrand, South Africa

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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..

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cervical High Grade Squamous Intraepithelial Lesion

Keywords

HSIL, CIN, HPV, HPV vaccination, gardasil, HIV, cervical dysplasia, LEEP, cervical cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

180 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Human Papillomavirus vaccine

Arm Type

Experimental

Arm Description

Participants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26.

Arm Title

Saline placebo

Arm Type

Placebo Comparator

Arm Description

The participants receive saline placebo at entry, week 4 and week 26.

Intervention Type

Biological

Intervention Name(s)

Human Papillomavirus vaccine

Other Intervention Name(s)

qHPV vaccine

Intervention Description

The participants receive the qHPV vaccine at entry, week 4 and week 26

Primary Outcome Measure Information:

Title

Cervical HSIL

Description

Time Frame

up to 52 weeks

Secondary Outcome Measure Information:

Title

Cervical Cytology

Description

Time Frame

Week 26

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HIV infection Women aged ≥ 18 years. Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3) For participants of reproductive potential, negative serum or urine pregnancy test 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: History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer Prior hysterectomy Cervical cryotherapy or LEEP/LEETZ within one year of entry. Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer Prior receipt of one or more doses of an HPV vaccine. Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry. 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). Hemophilia or other bleeding diatheses. 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. Breastfeeding Less than 3 months post-partum

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy J Wilkin, M.D. MPH

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Cynthia Firnhaber, M.D.

Organizational Affiliation

University or Witswatersrand

Official's Role

Study Chair

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32975556

Citation

Firnhaber C, Swarts A, Jezile V, Mulongo M, Goeieman B, Williams S, Faesen M, Michelow P, Wilkin T. Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial. Clin Infect Dis. 2021 Oct 5;73(7):e2211-e2216. doi: 10.1093/cid/ciaa1456.

Results Reference

derived

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

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