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

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

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.

Study Overview

• Status: Terminated
• Conditions: High Grade Anal Canal Intraepithelial Neoplasia; High Grade Vulvar Squamous Intraepithelial Lesion
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Other: Placebo Administration; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 27 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients	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.	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) Via Solicited Vaccine Reactogenicity by Arm	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.	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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anna Wald, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

General Publications

• Stankiewicz Karita HC, Hauge K, Magaret A, Mao C, Schouten J, Grieco V, Xi LF, Galloway DA, Madeleine MM, Wald A. Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Trial Protocol. JAMA Netw Open. 2019 Apr 5;2(4):e190819. doi: 10.1001/jamanetworkopen.2019.0819.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 9790 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2017-00151 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA213130 (U.S. NIH Grant/Contract); RG1001522 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No