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

NCT ID: NCT01928225

Last Updated: 2020-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-02
• Study Completion Date: 2018-03-01

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..

Conditions

Cervical High Grade Squamous Intraepithelial Lesion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Human Papillomavirus vaccine

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

Group Type: EXPERIMENTAL

Human Papillomavirus vaccine

Intervention Type: BIOLOGICAL

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

Saline placebo

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

Group Type: PLACEBO_COMPARATOR

Human Papillomavirus vaccine

Intervention Type: BIOLOGICAL

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

Interventions

Human Papillomavirus vaccine

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

Intervention Type: BIOLOGICAL

Other Intervention Names

qHPV vaccine

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role: lead

Responsible Party

Cynthia S Firnhaber

Technical Director of the Clinical HIV Research Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timothy J Wilkin, M.D. MPH

Role: STUDY_CHAIR

Weill Medical College of Cornell University

Cynthia Firnhaber, M.D.

Role: STUDY_CHAIR

University or Witswatersrand

References

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.

Reference Type: DERIVED

PMID: 32975556 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

QHPV-RTC

Identifier Type: -

Identifier Source: org_study_id