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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated 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.
Study Start Date :	September 2014
Estimated Primary Completion Date :	December 2016
Estimated Study Completion Date :	March 2017

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Cervical HSIL [ Time Frame: up to 52 weeks ]
   HSIL on cervical cytology or HSIL on cervical biopsy

Secondary Outcome Measures :

1. Cervical Cytology [ Time Frame: Week 26 and Week 52 ]
   Cervical cytology abnormalities according to the Bethesda scale.
2. Stored cervical swabs [ Time Frame: Week 0, 4, 26 and 52 ]
   Proportion of participants with stored cervical swabs for future HPV DNA testing at these time points.
3. Stored specimens from immunology subset participants [ Time Frame: Weeks 0, 4, 26 and 52 ]
   We will report the proportion of participants with stored cervical fluid, plasma, serum, PBMC, and whole blood lysate at these time points.
4. Subgroup analyses of primary outcome [ Time Frame: Weeks 26 and 52 ]
   Cervical HSIL at week 26 and 52 in women stratified by whether cervical HSIL is found on LEEP/LLETZ biopsy, and stratified by whether LEEP/LLETZ margins have HSIL detected.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Cynthia S Firnhaber, Technical Director of the Clinical HIV Research Unit, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier:	NCT01928225 History of Changes
Other Study ID Numbers:	QHPV-RTC
First Posted:	August 23, 2013
Last Update Posted:	May 13, 2016
Last Verified:	May 2016
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; Uterine Cervical Dysplasia; Precancerous Conditions; Neoplasms; Uterine Cervical Diseases	Uterine Diseases; Genital Diseases, Female; Vaccines; Immunologic Factors; Physiological Effects of Drugs