Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
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.
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.
DISEASE CHARACTERISTICS:

 •Healthy participants

 -  Deemed to be in good general health by history and physical examination

 •Resident of Guanacaste Province of Costa Rica and surrounding areas

 -  Must remain a resident for ≥ 6 months after the first study vaccination

 PATIENT CHARACTERISTICS:

 Age

 -  18 to 25

 Performance status

 •Not specified

 Life expectancy

 •Not specified

 Hematopoietic

 •Not specified

 Hepatic

 -  No history of chronic hepatitis requiring treatment

 -  No acute or chronic clinically significant hepatic function abnormality by physical
 examination or laboratory findings

 -  No known history of hepatitis A infection

 Renal

 -  No history of kidney disease requiring treatment

 -  No acute or chronic clinically significant kidney function abnormality by physical
 examination or laboratory findings

 Cardiovascular

 -  No acute or chronic clinically significant cardiovascular function abnormality by
 physical examination or laboratory findings Pulmonary

 -  No acute or chronic clinically significant pulmonary function abnormality by physical
 examination or laboratory findings Immunology

 -  No history of allergic disease

 -  No history of autoimmune disorder requiring treatment

 -  No history of allergic reaction (e.g., difficulty breathing) to any vaccine

 -  No suspected allergy or reaction likely to be exacerbated by a component of the study
 vaccines (e.g., 2-phenoxyethanol or neomycin)

 -  No hypersensitivity to latex

 -  No diagnosis or suspicion of any immunodeficient condition by medical history or
 physical examination Other

 -  Not pregnant or nursing

 ◦No delivery within the past 3 months

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception for 30 days before, during, and for
 60 days after completion of study treatment

 -  Able to speak or understand Spanish

 -  Mentally competent

 -  Able to undergo pelvic exam (i.e., no heavy bleeding [menstruation or otherwise] or
 heavy vaginal discharge)

 -  No history of cancer requiring treatment

 -  No history of diabetes requiring treatment

 -  No history of other chronic conditions requiring treatment

 -  No acute or chronic clinically significant neurologic function abnormality by physical
 examination or laboratory findings

 -  No other acute disease

 -  No fever ≥ 37.5º C

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  More than 6 months since prior chronic administration (i.e., > 14 days) of
 immune-modulating drugs

 -  More than 90 days since prior immunoglobulins

 -  More than 30 days since prior and no other concurrent investigational or
 non-registered vaccines

 -  More than 30 days since prior registered vaccines

 -  More than 8 days since prior routine meningococcal, hepatitis B, influenza, or
 diphtheria/tetanus vaccine

 -  No prior vaccination against hepatitis A

 -  No prior vaccination against human papillomavirus

 -  No prior monophosphoryl lipid A or AS04 adjuvant

 Chemotherapy

 •Not specified

 Endocrine therapy

 -  More than 6 months since prior chronic administration (i.e., > 14 days) of
 corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent)

 -  Concurrent inhaled or topical steroids allowed

 Radiotherapy

 •Not specified

 Surgery

 •No prior hysterectomy

 Other

 -  More than 6 months since prior chronic administration (i.e., > 14 days) of
 immunosuppressants

 -  More than 30 days since prior and no other concurrent investigational or
 non-registered drugs