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

Phase 4

Terminated

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

Interventions: Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
Other: Placebo Administration
Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	Laboratory Biomarker Analysis	Patients receive placebo IM at baseline, 2 months, and 6 months.
Arm I (recombinant human papillomavirus nonavalent vaccine)	Questionnaire Administration	Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.
Arm I (recombinant human papillomavirus nonavalent vaccine)	Recombinant Human Papillomavirus Nonavalent Vaccine	Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.
Arm II (placebo)	Placebo Administration	Patients receive placebo IM at baseline, 2 months, and 6 months.
Arm II (placebo)	Questionnaire Administration	Patients receive placebo IM at baseline, 2 months, and 6 months.
Arm I (recombinant human papillomavirus nonavalent vaccine)	Laboratory Biomarker Analysis	Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.

Primary Outcome Measures

Name	Time	Method
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients	Up to month 36	Persistence will be measured as two or more consecutive polymerase chain reaction (PCR) positive swabs for the same human papillomavirus (HPV) genotype. Will use Chi-Square test to compare the number of participants with the persistent infection in the vaccinated to unvaccinated group.

Secondary Outcome Measures

Name	Time	Method
Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL)	Up to month 36	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.
HPV Antibody Level	Up to month 36	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.
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm	Up to month 36	Will monitor safety by comparing type and frequency of AEs in the two study arms, graded according to the Food and Drug Administration criteria. Symptoms are reported at least once from any dose.

Locations (2): Fred Hutch/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, United States