Cervical Cancer, Nonneoplastic Condition, Precancerous Condition
Conditions
Keywords
human papilloma virus infection, cervical cancer, cervical intraepithelial neoplasia, HIV infection
Brief summary
RATIONALE: Vaccines made from virus proteins may help the body build an effective immune response to prevent cervical cancer. PURPOSE: This pilot study is looking at the side effects of a human papillomavirus vaccine and how well it works in preventing cervical cancer in women in India with HIV-1 infection.
Detailed description
OBJECTIVES: Primary * Assess the safety of the Gardasil® quadrivalent human papillomavirus (HPV) (types 6, 11, 16,18) virus-like-particle vaccine with vs without prior exposure to one or more of the HPV types in the vaccine in HIV-positive women in Chennai, India. * Determine the effect of the vaccine on HIV viral load and CD4+/CD8+ levels in these patients. * Determine the proportion of these patients who respond serologically to the HPV vaccine and the kinetics of their response. Secondary * Determine the prevalence and incidence of cervical intraepithelial neoplasia in these patients. * Determine the spectrum of cervical HPV types in these patients at baseline, 9 months, and 1 year after vaccination. OUTLINE: This is a multicenter study. Patients receive quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and once in weeks 8 and 24. Patients undergo cervical cell, buccal cell, and blood sample collection at baseline and periodically after vaccination for immunologic and virologic studies. Cervical cytology specimens are examined by polymerase chain reaction to detect HPV 6, 11, 16, or 18 DNA, as well as 35 other HPV types. Blood samples are analyzed for CD4+/CD8+ cell count, plasma HIV-1 RNA levels, and serum HPV antibody titers for HPV types 6, 11, 16, and 18. Some plasma samples will be stored for future HPV pseudovirion neutralization assays. After completion of study therapy, patients are followed periodically for up to 12 months.
Interventions
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
GENETICDNA analysis
Weeks 0, 2, 10, 26, and 52.
GENETICpolymerase chain reaction
Screening, week 36, and week 52.
OTHERcytology specimen collection procedure
Screening, week 36, and week 52.
PROCEDUREcolposcopic biopsy
Screening, week 36, and week 52.
Sponsors
National Cancer Institute (NCI)
The Emmes Company, LLC
AIDS Malignancy Consortium
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot before study entry * HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test * Meets 1 of the following criteria: * Nadir CD4 level of ≤ 350 cells/mm³ and receiving highly active antiretroviral therapy (HAART) for at least 6 months before study entry * Nadir CD4 level of \> 350 cells/mm³ and not receiving HAART at the time of study entry * No known history of high-grade CIN or cervical cancer PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * ANC \> 750 cells/mm³ * Hemoglobin ≥ 9.0 g/dL * Platelet count ≥ 100,000/mm³ * Serum creatinine ≤ 3 times upper limit of normal (ULN) * AST and ALT ≤ 3.0 times ULN * Conjugated (direct) bilirubin ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the site Investigator * No serious illness requiring systemic treatment and/or hospitalization within the past 45 days * No allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 45 days since prior systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin * Routine standard of care, including hepatitis B, influenza, and tetanus vaccines are allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0 | 52 weeks from study entry | Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients |
| Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count | Screening/Week 0, Weeks 2, 10, 26, and 52. | Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests |
| Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28 | Week 28 | Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline |
| Number of Patients With a Significant Increase in HIV Viral Load | Screening/week 0, weeks, 2, 10, 26 and 52 | Number of patients with a significant increase in HIV viral load defined as \> 1 log increase in HIV load from baseline on 2 consecutive occasions |
| Number of Patients With Detectable Antibodies to HPV-6 | 28 weeks | Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline |
| Number of Patients With Detectable Antibodies to HPV-11 | 28 weeks | Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline |
| Number of Patients With Detectable Antibodies to HPV-18 | 28 weeks | Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gardasil Vaccination Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine: Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
DNA analysis: Weeks 0, 2, 10, 26, and 52.
polymerase chain reaction: Screening, week 36, and week 52.
cytology specimen collection procedure: Screening, week 36, and week 52.
colposcopic biopsy: Screening, week 36, and week 52. | 150 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 24 |
Baseline characteristics
| Characteristic | Gardasil Vaccination |
|---|---|
| Age, Continuous | 30.8 years STANDARD_DEVIATION 5.2 |
| Sex: Female, Male Female | 150 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 145 / 150 |
| serious Total, serious adverse events | 4 / 150 |
Outcome results
Primary
Number of Patients With a Significant Increase in HIV Viral Load
Number of patients with a significant increase in HIV viral load defined as \> 1 log increase in HIV load from baseline on 2 consecutive occasions
Time frame: Screening/week 0, weeks, 2, 10, 26 and 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With a Significant Increase in HIV Viral Load | 7 participants |
Primary
Number of Patients With Detectable Antibodies to HPV-11
Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline
Time frame: 28 weeks
Population: Per-protocol population of participants with undetectable antibodies for HPV-11 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With Detectable Antibodies to HPV-11 | 110 participants |
Primary
Number of Patients With Detectable Antibodies to HPV-18
Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline
Time frame: 28 weeks
Population: Per-protocol population of participants with undetectable HPV-18 antibodies at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With Detectable Antibodies to HPV-18 | 94 participants |
Primary
Number of Patients With Detectable Antibodies to HPV-6
Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline
Time frame: 28 weeks
Population: Per-protocol participants with undetectable antibodies to HPV-6 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With Detectable Antibodies to HPV-6 | 88 participants |
Primary
Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28
Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline
Time frame: Week 28
Population: Per-protocol population with undetectable HPV-16 levels at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28 | 95 participants |
Primary
Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count
Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests
Time frame: Screening/Week 0, Weeks 2, 10, 26, and 52.
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count | 11 participants |
Primary
Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0
Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients
Time frame: 52 weeks from study entry
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil Vaccination | Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0 | 6.0 Grade 3/4 adverse events per 100 patient |