Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Prevention Closed 18 to 25 NCI NCI-04-C-N191 NCI-590299/009, GSK-590299/009, NCT00128661

Objectives

Primary

1. 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

1. 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.
2. Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status.
3. 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.
4. 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.
5. Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants.
6. 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.

Entry Criteria

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

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

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

Expected Enrollment

Approximately 7,500 participants will be accrued for this study.

Outcomes

Histopathologically confirmed, incident CIN2+ associated with an HPV16 or HPV18 infection

Occurrence and intensity of solicited local adverse events (AE) and occurrence (either onset or aggravation) of solicited general AEs including urticaria within 30 minutes after each vaccination and over all vaccinations
Occurrence and intensity of solicited local AE and solicited general AE between day 3 and 6 after each vaccination and over all vaccinations
Occurrence of unsolicited AEs and severe AEs at month 0 through month 48
Outcome of all pregnancies

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.

Hildesheim A, Herrero R, Wacholder S, et al.: Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA 298 (7): 743-53, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Rolando Herrero, MD, Protocol chair		Ph: 506-665-0242 Email: rherrero@amnet.co.cr
Allan Hildesheim, PhD, Principal investigator		Ph: 301-496-1691 Email: hildesha@mail.nih.gov

Registry Information
Official Title		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
Trial Start Date		2004-06-28
Registered in ClinicalTrials.gov		NCT00128661
Date Submitted to PDQ		2005-07-21
Information Last Verified		2007-02-26