Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
Condition: Cervical Cancer; Precancerous Condition
MeSH terms: Uterine Cervical Neoplasms; Neoplasms; Uterine Cervical Dysplasia; Precancerous Conditions
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing,
      or coming back. Vaccines may help the body build an effective immune response against human
      papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or
      cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective
      than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.

      PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how
      well it works compared to hepatitis A vaccine in preventing cervical intraepithelial
      neoplasia or cervical cancer in younger healthy participants.
    

Detailed description: 
      OBJECTIVES:

      Primary

      •Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1
      virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3
      cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive
      cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger
      healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the
      corresponding HPV type at months 0 and 6.

      Secondary

        -  Determine the duration of protection against HPV 16 or HPV 18 cervical infection in
           participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.

        -  Determine the safety of this vaccine in these participants, regardless of their initial
           HPV 16/18 DNA status.

        -  Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared
           with control in preventing CIN2+ associated with any oncogenic HPV type cervical
           infection in participants who are negative for HPV DNA by PCR for the corresponding HPV
           type at months 0 and 6.

        -  Compare the efficacy of the candidate vaccine with control in preventing CIN2+
           associated with HPV 16 or HPV 18 cervical infection, detected within the lesional
           component of the cervical tissue specimen by PCR, in participants who are negative for
           HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked
           immunosorbent assay (ELISA) at month 0.

        -  Compare the efficacy of the candidate vaccine with control in preventing persistent HPV
           16 or HPV 18 cervical infection in these participants.

        -  Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4
           monoclonal antibody inhibition enzyme immunoassay in the first 600 participants
           randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.

      OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants
      are randomized to 1 of 2 treatment arms.

        -  Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04
           vaccine intramuscularly (IM) once in months 0, 1, and 6.

        -  Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and
           6.

      After completion of study treatment, participants are followed at 6 months and then at least
      annually for 3 years.

      PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.
    

Intervention name(s): human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine; hepatitis A inactivated virus vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Three doses of Cervarix vaccine administered on a 0, 1, 6-month schedule; Three doses of Havrix vaccine administered on a 0, 1, 6-month schedule
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: cervical intraepithelial neoplasia grade 2; cervical cancer; cervical intraepithelial neoplasia grade 3