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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-00841 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| AMC-099 | Other Identifier | AIDS Malignancy Consortium | |
| AMC-099 | Other Identifier | CTEP | |
| UM1CA121947 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| University of Arkansas | OTHER |
| AIDS and Cancer Specimen Resource | OTHER |
| Merck Sharp & Dohme LLC |
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This randomized phase III trial studies how well human papillomavirus (HPV) vaccine therapy works in reducing high-grade cervical lesions in patients with human immunodeficiency virus (HIV) and HPV. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill the HPV virus and prevent cervical lesions from developing or coming back after being removed.
At screening, potential participants will be tested for cervical human papillomavirus (HPV) infection (GeneXpert hrHPV assay and HPV DNA PCR) and undergo cervical colposcopy to confirm the absence of cervical cancer. If eligible, the participant will be randomized to receive either the 9-valent HPV vaccine or saline placebo.
Participants will return 4 and 26 weeks later for the second dose of vaccine or placebo. At week 4, participants will have cervical colposcopy and undergo cryotherapy or loop electrosurgical excisional procedure (LEEP) as appropriate. Participants undergoing cervical cryotherapy will have cervical biopsies before the treatment. Participants will be followed with HPV testing (Gene Xpert and HPV DNA PCR) at weeks 26, 52, 78, and 104, and will have cervical cytology and colposcopy with biopsies at weeks 26, 52, and 104.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I, recombinant HPV 9-valent vaccine | Experimental | Patients receive Recombinant Human Papillomavirus Nonavalent Vaccine (Gardasil 9) IM at baseline, 4, and 26 weeks in the absence of disease progression or unacceptable toxicity, with sample collection for Laboratory Biomarker Analysis. |
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| Arm II, saline | Placebo Comparator | Patients receive saline placebo vaccine IM at baseline, 4, and 26 weeks, with sample collection for Laboratory Biomarker Analysis. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of cervical high-grade squamous intraepithelial lesions (HSIL) or cervical cancer | For each arm (vaccine and placebo), the event rate will be estimated using its point estimate and 95% Poisson confidence intervals. Poisson regression analyses will be used to compare the two arms with respect to event rate. In addition, time to event from week 4 to 52 will be described using the Kaplan-Meier method for each arm, and the two arms will be compared with respect to time to event using the log-rank test. | After week 4 study visit to week 52 post-randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of cervical HSIL from weeks 52-104 | The event rate for each arm from week 52 to week 104 for women who are event-free at 52 weeks will be estimated using its point estimate and 95% Poisson confidence interval. Poisson regression will be used to compare the two groups with respect to the event rate from week 52 to 104. | After week 52 to week 104 |
| Measure | Description | Time Frame |
|---|---|---|
| HPV type distributions | Will characterize the HPV type distribution in baseline histology specimens and compare this to the types observed among incident cervical and vulvar HSIL lesions. Specifically, will compare the number and proportion of vaccine-type and non-vaccine type lesions between arms. | Up to week 104 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carla Chibwesha | University of Witwatersrand, South Africa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moi University School of Medicine | Eldoret | Kenya | ||||
| UNC Project Malawi |
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| INDUSTRY |
| The Emmes Company, LLC | INDUSTRY |
| University of California, Los Angeles | OTHER |
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| Recombinant Human Papillomavirus Nonavalent Vaccine | Biological | Given IM |
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| Saline | Other | Given IM |
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| Role of baseline types and quantity of HPV as predictors of sustained absence | Poisson regression analyses will be used to determine if baseline HPV types are associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of presence of HSIL at baseline as a predictor of sustained absence | Poisson regression analyses will be used to determine if the presence of HSIL at baseline is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of CD4+ cell count as a predictor of sustained absence | Poisson regression analyses will be used to determine if baseline CD4+ cell count is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of plasma HIV-1 RNA as a predictor of sustained absence | Poisson regression analyses will be used to determine if baseline plasma HIV-1 RNA count is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of ART use as a predictor of sustained absence | Poisson regression analyses will be used to determine if ART use is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of age as a predictor of sustained absence | Poisson regression analyses will be used to determine if age is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of sexual behavior as a predictor of sustained absence | Poisson regression analyses will be used to determine if sexual behavior is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Role of vaccination use as a predictor of sustained absence | Poisson regression analyses will be used to determine if vaccine use is associated with of sustained absence of cervical HSIL and clearance of HPV infections after cryotherapy or LEEP. This analysis will also control for use of LEEP or cryotherapy. | At baseline and week 4 |
| Incident cervical vaccine type HPV infections defined as infections at 2 consecutive timepoints and assessed using type specific HPV DNA polymerase chain reaction (PCR) | Vaccine and placebo participants will be compared with respect to these proportions using the chi-square test corrected for continuity. | Up to week 104 |
| Abnormal cervical cytology | The proportion of women with abnormal cervical cytology at baseline, week 26, 52, and 104 will be reported and compared between arms. | Baseline, week 26, 52, and 104 |
| Prevalent vulvar HSIL or cancer | The prevalence of vulvar HSIL or cancer at baseline will be estimated using the binomial proportion and its 95% confidence interval. | Up to week 4 |
| Incident vulvar HSIL or cancer | The proportion of women who acquire vulvar HSIL or cancer among those negative for vulvar HSIL or cancer at baseline for both intervention arms will be estimated as a binomial proportion for both groups. The chi-square test corrected for continuity will be used to compare arms with respect to the proportions who acquire vulvar HSIL during the study. | Up to week 104 |
| Clinical and demographic factors associated with incident vulvar HSIL or cancer | Logistic regression analyses will be used to evaluate associations with incident vulvar HSIL or cancer acquisition with clinical and demographic factors and arm. | Up to week 104 |
| HPV strain variant analysis of cervical and vulvar HSIL specimens |
For study participants who have the same HPV type in HSIL specimens at baseline and follow-up time points, sequencing will be performed to determine whether or not HSIL is caused by an identical HPV strain. Will use all available pairs of baseline and follow-up HSIL caused by the same HPV type. Will report the proportion of these pairs with the same HPV strain in both treatment arms. Additionally, will report the rates of HSIL caused by new vaccine type infections. We will compare the two study groups using a chi-square test. This will be a descriptive analysis only as no sufficient data on which to power this analysis. |
| Up to week 104 |
| Tissue microarray library of cervical specimens for biomarker analysis and discovery | Specimen banking objective. There is no pre-specified statistical analysis plan for this objective. Any future studies using these specimens will need to receive separate approval by NCI and CTEP. | Up to week 104 |
| hrHPV type distribution in the anus | McNemar's chi-square test to compare the prevalence of that type in the anus and cervix will be used. For each hrHPV type, chi-square analyses will be used to compare the two HPV vaccination groups with respect to the distribution of that type in the (anus, cervix). Will report the proportion of incident cervical infections that were preceded by anal detection of the same type. | Up to week 104 |
| hrHPV type prevalence in the anus | McNemar's chi-square test to compare the prevalence of that type in the anus and cervix will be used. For each hrHPV type, chi-square analyses will be used to compare the two HPV vaccination groups with respect to the distribution of that type in the (anus, cervix). Will report the proportion of incident cervical infections that were preceded by anal detection of the same type. | Up to week 104 |
| Vaccine-induced antibody titers | Will explore the antibody titers for the vaccine type found in the HSIL in these women as compared to those without HSIL caused by that type. Analysis of vaccine titers between those with incident vaccine type HPV infections that persist for 2 or more study visits and those that do not will be performed. | Up to week 104 |
| Lilongwe |
| Malawi |
| African Cancer Institute at Stellenbosch | Cape Town | South Africa |
| University of the Witwatersrand | Johannesburg | South Africa |
| Uganda Cancer Institute | Kampala | Uganda |
| University of Zimbabwe | Harare | Zimbabwe |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000634046 | Human Papillomavirus Recombinant Vaccine nonavalent |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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