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

• ClinicalTrials.gov Identifier: NCT01928225
• Recruitment Status: Completed
• First Posted: August 23, 2013
• Results First Posted: June 24, 2020
• Last Update Posted: June 24, 2020
• Sponsor: University of Witwatersrand, South Africa
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Cynthia S Firnhaber, University of Witwatersrand, South Africa

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.

Condition or disease	Intervention/treatment	Phase
Cervical High Grade Squamous Intraepithelial Lesion	Biological: Human Papillomavirus vaccine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: September 2, 2014
• Actual Primary Completion Date: November 30, 2017
• Actual Study Completion Date: March 1, 2018

Arms and Interventions

Arm	Intervention/treatment
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 Name: 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 Name: qHPV vaccine

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

University of Witwatersrand, South Africa

Merck Sharp & Dohme Corp.

Investigators

• Study Chair: Timothy J Wilkin, M.D. MPH; Weill Medical College of Cornell University
• Study Chair: Cynthia Firnhaber, M.D.; University or Witswatersrand

  Study Documents (Full-Text)

Documents provided by Cynthia S Firnhaber, University of Witwatersrand, South Africa:

Study Protocol and Statistical Analysis Plan  [PDF] November 8, 2014

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Cynthia S Firnhaber, Technical Director of the Clinical HIV Research Unit, University of Witwatersrand, South Africa
• ClinicalTrials.gov Identifier: NCT01928225
• Other Study ID Numbers: QHPV-RTC
• First Posted: August 23, 2013
• Results First Posted: June 24, 2020
• Last Update Posted: June 24, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Cynthia S Firnhaber, University of Witwatersrand, South Africa:

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

Additional relevant MeSH terms:

Squamous Intraepithelial Lesions of the Cervix; Carcinoma, Squamous Cell; Carcinoma in Situ; Uterine Cervical Dysplasia; Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Vaccines; Immunologic Factors; Physiological Effects of Drugs