High Grade Anal Canal Intraepithelial NeoplasiaPhase 4NCT03051516

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

A Phase 4 study testing Laboratory Biomarker Analysis, Questionnaire Administration and Recombinant Human Papillomavirus Nonavalent Vaccine in people with High Grade Anal Canal Intraepithelial Neoplasia and High Grade Vulvar Squamous Intraepithelial Lesion, run by Fred Hutchinson Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 27 to 69 years
Conditions the study is for: High Grade Anal Canal Intraepithelial Neoplasia, High Grade Vulvar Squamous Intraepithelial Lesion
What is being tested?: Laboratory Biomarker Analysis, Questionnaire Administration and Recombinant Human Papillomavirus Nonavalent Vaccine
Type of treatment: Vaccines
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 188 participants
Where: 2 sitesUnited States
Study dates: 1 Aug 2017to 31 Dec 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 27 to 69 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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

Other trials in United States

About this study

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

Read the 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.

Conditions: High Grade Anal Canal Intraepithelial Neoplasia, High Grade Vulvar Squamous Intraepithelial Lesion
Being tested: Laboratory Biomarker Analysis, Placebo Administration, Questionnaire Administration, Recombinant Human Papillomavirus Nonavalent Vaccine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given IM
Questionnaire AdministrationOther
Ancillary studies
Recombinant Human Papillomavirus Nonavalent VaccineBiological
Also called Gardasil 9, Nonavalent HPV Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent Vaccine
Given IM

Study groups in NCT03051516
Study group	Role	What they receive
Arm I (recombinant human papillomavirus nonavalent vaccine)	Experimental	Patients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months. Receives: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Arm II (placebo)	Placebo comparator	Patients receive placebo IM at baseline, 2 months, and 6 months. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to month 36

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: Up to month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 201731 Dec 2022

First posted13 Feb 2017
Study start1 Aug 2017
Primary completion31 Dec 2022
Study completion31 Dec 2022

Why it stopped: The study was terminated early due to futility.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for High Grade Anal Canal Intraepithelial NeoplasiaStudies of the same condition, open and under way.
More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 188 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03051516
Sponsor's protocol ID: 9790
Other IDs: NCI-2017-00151, 9790, R01CA213130, RG1001522
Status last verified: Jan 2024
First submitted: 9 Feb 2017
Last updated: 28 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Stankiewicz Karita HC, Magaret AS, Doody DR, Schouten JT, Mao C, Huh WK, Grieco VS, Seymour MA, Varon D, Shrader KH, Xi LF, Galloway DA, Wald A, Madeleine MM. Nonavalent HPV vaccine to prevent recurrent anal or vulvar high-grade squamous intraepithelial lesions (VIVA trial): A randomized, double-blind, placebo-controlled trial. Int J Cancer. 2026 Jun 1;158(11):2983-2994. doi: 10.1002/ijc.70366. Epub 2026 Feb 13.
PubMed 41685810
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.
PubMed 30977845

Study at a glance

From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: HPV Vaccine to Interrupt Progression of Vulvar and Anal Neoplasia (VIVA) Trial: A Randomized, Double-Blind, Placebo-Controlled Trial
ClinicalTrials.gov ID: NCT03051516
Acronym / sponsor ID: 9790
Conditions: High Grade Anal Canal Intraepithelial Neoplasia, High Grade Vulvar Squamous Intraepithelial Lesion
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated early due to futility.
Enrolment: 188 participants (actual)
Lead sponsor: Fred Hutchinson Cancer CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 1 Aug 2017 (actual)
Primary completion: 31 Dec 2022 (actual)
Study completion: 31 Dec 2022 (actual)
First posted: 13 Feb 2017 (actual)
Results: Posted 28 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Arm I (recombinant human papillomavirus nonavalent vaccine)	Experimental	Other: Laboratory Biomarker Analysis, Other: Questionnaire Administration, Biological: Recombinant Human Papillomavirus Nonavalent VaccinePatients receive recombinant human papillomavirus nonavalent vaccine IM at baseline, 2 months, and 6 months.
Arm II (placebo)	Placebo comparator	Other: Laboratory Biomarker Analysis, Other: Placebo Administration, Other: Questionnaire AdministrationPatients receive placebo IM at baseline, 2 months, and 6 months.

Who may qualify

Ages: 27 to 69 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Laboratory Biomarker AnalysisCorrelative studies	Other	Arm I (recombinant human papillomavirus nonavalent vaccine), Arm II (placebo)
Placebo AdministrationGiven IM	Other	Arm II (placebo)
Questionnaire AdministrationAncillary studies	Other	Arm I (recombinant human papillomavirus nonavalent vaccine), Arm II (placebo)
Recombinant Human Papillomavirus Nonavalent VaccineAlso: Gardasil 9, Nonavalent HPV Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent VaccineGiven IM	Biological	Arm I (recombinant human papillomavirus nonavalent vaccine)

Primary outcome

Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients
Time frame: 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.

3 secondary outcomes

Time to Recurrence of Anogenital High Grade Squamous Intraepithelial Lesion (HSIL)
Time frame: Up to month 36
Incidence of Adverse Events (AEs) Via Solicited Vaccine Reactogenicity by Arm
Time frame: Up to month 36
HPV Antibody Level
Time frame: Up to month 36

Results and safety

Results posted to the registry on 28 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine)	93	38
Arm II (Placebo)	95	42

Primary outcome: Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients

Time frame: Up to month 36. Count of participants. Unit: Participants

Measure	Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) n = 53	Arm II (Placebo) n = 64
HPV16 persistence identified	7	9
HPV18/45 persistence identified	3	5
HPV31/33/52/58 persistence identified	3	11
HPV33/39/51/56/59 persistence identified	4	8
Overall high-risk HPV persistence identified	13	21
High-risk HPV persistence NOT identified	23	10

Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) vs Arm II (Placebo): p = 0.89, Chi-squared
Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) vs Arm II (Placebo): p = 0.65, Chi-squared
Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine) vs Arm II (Placebo): p = 0.056, Chi-squared

Population analysed: Participants were included in this analysis if they had 2 or more HPV DNA PCR results from swabs collected after the baseline swab. Of the 185 participants in the baseline population, 117 were included in this analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 42 months, from enrollment visit (Month 0) to final follow-up at Month 42.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm I (Recombinant Human Papillomavirus Nonavalent Vaccine)	19 of 91 (20.9%)	60 of 91 (65.9%)	5 of 91
Arm II (Placebo)	16 of 94 (17%)	58 of 94 (61.7%)	2 of 94

Limitations and caveats (from the sponsor): An interim analysis found the intervention to be futile. Therefore, the VIVA trial was ended effective July 31st, 2022, for the University of Washington clinic, and December 31st, 2022, for the University of Alabama Birmingham clinic. Participants were offered the choice of continuing any outstanding visits until the end of the study at the respective sites.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41685810Stankiewicz Karita HC, Magaret AS, Doody DR, Schouten JT, Mao C, Huh WK, Grieco VS, Seymour MA, Varon D, Shrader KH, Xi LF, Galloway DA, Wald A, Madeleine MM. Nonavalent HPV vaccine to prevent recurrent anal or vulvar high-grade squamous intraepithelial lesions (VIVA trial): A randomized, double-blind, placebo-controlled trial. Int J Cancer. 2026 Jun 1;158(11):2983-2994. doi: 10.1002/ijc.70366. Epub 2026 Feb 13.
Derived from this study: PubMed 30977845Stankiewicz 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Anna Wald principal investigator

Fred Hutch/University of Washington Cancer Consortium

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Persistent High-risk Infection Among Vaccine Compared With Placebo Recipients (time frame: Up to month 36). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03051516, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.