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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Cynthia S Firnhaber, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier:
NCT01928225
First received: August 20, 2013
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Cervical High Grade Squamous Intraepithelial Lesion
Biological: Human Papillomavirus vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by University of Witwatersrand, South Africa:

Primary Outcome Measures:
  • Cervical HSIL [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
    HSIL on cervical cytology or HSIL on cervical biopsy


Secondary Outcome Measures:
  • Cervical Cytology [ Time Frame: Week 26 and Week 52 ] [ Designated as safety issue: No ]
    Cervical cytology abnormalities according to the Bethesda scale.

  • Stored cervical swabs [ Time Frame: Week 0, 4, 26 and 52 ] [ Designated as safety issue: No ]
    Proportion of participants with stored cervical swabs for future HPV DNA testing at these time points.

  • Stored specimens from immunology subset participants [ Time Frame: Weeks 0, 4, 26 and 52 ] [ Designated as safety issue: No ]
    We will report the proportion of participants with stored cervical fluid, plasma, serum, PBMC, and whole blood lysate at these time points.

  • Subgroup analyses of primary outcome [ Time Frame: Weeks 26 and 52 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 180
Study Start Date: September 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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..

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01928225

Locations
South Africa
Clinical HIV Research Unit
Johannesburg, Gauteng, South Africa, 2092
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

No publications provided

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
Study First Received: August 20, 2013
Last Updated: September 22, 2014
Health Authority: South Africa: Medicines Control Council

Keywords provided by University of Witwatersrand, South Africa:
HSIL
CIN
HPV
HPV vaccination
gardasil
HIV
cervical dysplasia
LEEP
cervical cancer

Additional relevant MeSH terms:
Uterine Cervical Dysplasia
Precancerous Conditions
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on October 02, 2014