Clinical Trials /

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

NCT03051516

Description:

This randomized 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.

Related Conditions:
  • Anal Neoplasm
  • Vulvar Squamous Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: HPV Vaccine Therapy in Interrupting Progression in Patients With High-Grade Vulvar or Anal Lesions
  • Official Title: HPV Vaccine to Interrupt Progression of Vulvar and Anal Neoplasia (VIVA) Trial: A Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trial IDs

  • ORG STUDY ID: 9790
  • SECONDARY ID: NCI-2017-00151
  • SECONDARY ID: 9790
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: R01CA213130
  • NCT ID: NCT03051516

Conditions

  • High Grade Anal Canal Squamous Intraepithelial Neoplasia
  • Vulvar High Grade Squamous Intraepithelial Lesion

Interventions

DrugSynonymsArms
Recombinant Human Papillomavirus Nonavalent VaccineGardasil 9, Nonavalent HPV VLP Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent VaccineArm I (recombinant human papillomavirus nonavalent vaccine)

Purpose

This randomized 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

      PRIMARY OBJECTIVES:

      I. Test if the recombinant human papillomavirus nonavalent vaccine (9vHPV vaccine) delivered
      after treatment for high grade squamous intraepithelial lesion (HSIL) reduces the risk of
      histologically confirmed recurrent neoplastic lesions (HSIL) by 50% in the vaccinated versus
      (vs.) placebo arms.

      II. Evaluate safety of the HPV vaccine in HSIL participants.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (recombinant human papillomavirus nonavalent vaccine)ExperimentalPatients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.
  • Recombinant Human Papillomavirus Nonavalent Vaccine
Arm II (placebo)Placebo ComparatorPatients receive placebo IM at baseline, 2 months, and 6 months.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Age 27- 69 at enrollment
    
              -  Histologically confirmed diagnosis of initial or recurrent anal or vulvar high-grade
                 squamous intraepithelial lesion 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 one time, >= 2 months after therapy
    
              -  Resident in the area and willing to attend up to 7 clinic visits for a 36-month period
                 at the Virology Research Clinic (VRC)
    
              -  Sexually active women of child-bearing potential must be willing to use effective
                 contraception through month 7 of the study
    
              -  If 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
          
    Maximum Eligible Age:69 Years
    Minimum Eligible Age:27 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Time to recurrence of anogenital high grade squamous intraepithelial lesion (HSIL)
    Time Frame:Up to month 36
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Incidence of adverse events (AEs) graded according to the Food and Drug Administration criteria
    Time Frame:Up to month 36
    Safety Issue:
    Description:Will monitor safety by comparing type and frequency of AEs in the two study arms.
    Measure:Human papillomavirus (HPV) persistence
    Time Frame:Up to month 36
    Safety Issue:
    Description:Will evaluate whether risk of recurrence is more frequent among those with HPV persistence. Persistence will be measured by HPV genotype or HPV16 variant lineage from swab samples collected at months 0, 18, and 36. Will use Cox proportional hazards, but including a time-dependent covariate of HPV persistence by deoxyribonucleic acid detection from swab samples.
    Measure:HPV antibody level
    Time Frame:Up to month 36
    Safety Issue:
    Description: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.
    Measure:Frequency of HSIL recurrence
    Time Frame:Up to month 36
    Safety Issue:
    Description:Will compare the rate of recurrence in each arm of the study. Will include all recurrences, not just first recurrences using Poisson regression with a robust variance estimate, comparing the total number of recurrences for each arm over the total follow-up per arm.

    Details

    Phase:Phase 4
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Fred Hutchinson Cancer Research Center

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