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Phase III Randomized Study of a Human Papillomavirus 16/18 L1 Virus-Like
Particle/AS04 Vaccine Versus a Control for the Prevention of Grade 2 or
3 Cervical Intraepithelial Neoplasia, Adenocarcinoma in Situ of the
Cervix, or Invasive Cervical Cancer in Younger Healthy Participants
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
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Protocol IDs
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Phase III
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Prevention
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Closed
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18 to 25
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NCI
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NCI-04-C-N191 NCI-590299/009, GSK-590299/009, NCT00128661
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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.
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 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 Surgery 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 Performance status Life expectancy Hematopoietic 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 7500Approximately 7,500 participants will be accrued for this study. Outcomes Primary Outcome(s)Histopathologically confirmed, incident CIN2+ associated with an HPV16 or HPV18 infection
Secondary Outcome(s)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. Published ResultsHildesheim 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 | | | | Allan Hildesheim, PhD, Principal investigator | | | |
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 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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