HPV Vaccine Therapy in Interrupting Progression in Patients With High-Grade Vulvar or Anal Lesions

Study Overview
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Brief Summary
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This phase IV trial studies how well human papillomavirus (HPV) vaccine therapy works in interrupting progression in patients with high-grade vulvar or anal lesions. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill tumor cells and decrease the chance of vulvar or anal lesions to progress or come back.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at baseline, 2 months, and 6 months. ARM II: Patients receive placebo IM at baseline, 2 months, and 6 months. After completion of study treatment, patients are followed up at months 7, 12, 18, 24, 36, and 42.

Official Title
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HPV Vaccine to Interrupt Progression of Vulvar and Anal Neoplasia (VIVA) Trial: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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High Grade Anal Canal Intraepithelial Neoplasia, High Grade Vulvar Squamous Intraepithelial Lesion

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Other: Placebo Administration
* Other: Questionnaire Administration
* Biological: Recombinant Human Papillomavirus Nonavalent Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of initial or recurrent anal or vulvar high-grade squamous intraepithelial lesion (AIN2/3 or VIN2/3) diagnosed on or after 1/1/2014; study pathologist will use p16 staining as needed to rule out low-grade squamous intraepithelial lesion (LSIL) disease >= 2 months since last therapy for HSIL No clinical evidence of HSIL on screening examination; if HSIL is suspected, a biopsy will be done to exclude HSIL; patients whose screening visit reveals HSIL on biopsy, may be re-screened >= 2 months after therapy Resident in the catchment area of the clinics and willing to attend up to 8 clinic visits for a 36-month period Sexually active women of child-bearing potential must be willing to use effective contraception through month 7 of the study If human immunodeficiency virus (HIV) positive, receipt of anti-retroviral therapy continuously for at least 6 months prior to enrollment Ability to give informed consent Willingness to sign medical records release form and tissue release form Exclusion Criteria: Currently pregnant Chemotherapy (current, within the last month, or anticipated in the next 7 months) Prior history of invasive HPV-related anogenital cancer (cervical, vaginal, vulvar, penile, or anal cancer), or oropharyngeal cancer (base of tongue, tonsil); prior cancer at other sites (including most of oral cavity) or larynx are not exclusions Unstable medical condition (e.g., another malignancy requiring treatment, malignant hypertension, poorly controlled diabetes, another cancer except for fully excised non-melanoma skin cancer) Prior HPV vaccination Known allergy or intolerance to lidocaine Currently participating in an interventional research study related to HPV, except the Anal Cancer HSIL Outcomes Research (ANCHOR) study (NCT02135419) Any other condition which, in the opinion of the investigator, may compromise the subject's ability to follow study procedures and safely complete the study

Ages Eligible for Study
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Minimum Age: 27 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (recombinant human papillomavirus nonavalent vaccine)<br>Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Biological: Recombinant Human Papillomavirus Nonavalent Vaccine<br>* Given IM<br>* Other names: Recombinant Human Papillomavirus 9-valent Vaccine;|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo IM at baseline, 2 months, and 6 months. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Placebo Administration<br>* Given IM<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to persistent high-risk infection among vaccine compared with placebo recipients | Persistence will be measured as two or more consecutive polymerase chain reaction positive swabs for the same human papillomavirus (HPV) genotype. Will use Cox proportional hazards to compare time start of interval for the persistent infection in the vaccinated to unvaccinated group. | Up to month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrence of anogenital high grade squamous intraepithelial lesion (HSIL) | Will compare vaccine and placebo recipients. Will evaluate differences in the hazard of recurrence using Cox proportional hazards in the intention to treat population and the per protocol population. | Up to month 36 | 
| Incidence of adverse events (AEs) graded according to the Food and Drug Administration criteria | Will monitor safety by comparing type and frequency of AEs in the two study arms. | Up to month 36 | 
| HPV antibody level | Will evaluate placebo and vaccine recipients separately. Will assess whether presence and amount of HPV antibody, detected at baseline in the placebo arm, is protective against recurrence. For the vaccine arm, will assess whether magnitude of vaccine antibody levels month 1 following the third vaccination in the vaccine arm affects recurrence. | Up to month 36 |