Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants

A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia (CIN2, CIN3, Adenocarcinoma In Situ [AIS] and Invasive Cervical Cancer) Associated With HPV 16 or HPV 18 Cervical Infection in Healthy Young Adult Women in Costa Rica.

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