Cervical High Grade Squamous Intraepithelial LesionPhase 2NCT01928225
Randomized, Double Blind Trial of the Quadrivalent HPV Vaccine to Improve Responses to LEEP Treatment of Cervical HSIL
A Phase 2 study testing Human Papillomavirus vaccine in people with Cervical High Grade Squamous Intraepithelial Lesion, run by University of Witwatersrand, South Africa.
Trial summary
Cervical cancer occurs commonly in HIV-infected women in South Africa. These women have poor response to treatment of cervical cancer precursors. This study will test whether giving the quadrivalent vaccine to women prior to surgical treatment of the cervical cancer precursor will improve outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical High Grade Squamous Intraepithelial Lesion
- What is being tested?
- Human Papillomavirus vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- 2 Sep 2014to 1 Mar 2018
- Phase
- Phase 2
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infection
- Women aged ≥ 18 years.
- Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3)
- For participants of reproductive potential, negative serum or urine pregnancy test
- All study participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) during study participation (from the time of study entry until week 52).
Who cannot join
- History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer
- Prior hysterectomy
- Cervical cryotherapy or LEEP/LEETZ within one year of entry.
- Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer
- Prior receipt of one or more doses of an HPV vaccine.
- Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry.
Show all 11Show fewer
- Known allergy/sensitivity or any hypersensitivity to yeast or any of the components of the study product or its formulation (see section 5.2 for a list of components).
- Hemophilia or other bleeding diatheses.
- Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, other than inhaled corticosteroids or prednisone ≤ 10 mg (or equivalent) , investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.
- Breastfeeding
- Less than 3 months post-partum
About this study
Official title: A Randomized, Placebo-controlled Trial of Pre-treatment HPV Vaccination on Outcomes to LEEP Treatment of Cervical High Grade Squamous Intraepithelial Lesions in HIV-infected Women.
Cervical cancer occurs commonly in HIV-infected women in South Africa. These women have poor response to treatment of cervical cancer precursors. This study will test whether giving the quadrivalent vaccine to women prior to surgical treatment of the cervical cancer precursor will improve outcomes. We hypothesize that pre-treatment HPV vaccine will result in a reduced occurrence or cervical cancer precursors in follow-up.
Read the detailed description
This is a single-center, randomized, double-blinded, placebo-controlled, phase II trial of the quadrivalent human papillomavirus vaccine (qHPV) in HIV-infected women to prevent occurrence of cervical HSIL after LEEP/LLETZ. Participants will undergo colposcopy with directed biopsies, cervical cytology, and stored HPV testing prior to vaccination. Participants will be randomized to the quadrivalent vaccine or saline placebo to be given at entry, week 4, and week 26. Women will have LEEP treatment at week 4. Participants will be seen in follow-up for cervical cytology, colposcopy with directed biopsies at weeks 26 and 52, and stored HPV specimens. Treatment assignment will be unblinded after study follow-up is completed for the last study participant. Women aged 45 or less randomized to placebo will be offered open label HPV vaccine after the study is concluded..
- Being tested
- Human Papillomavirus vaccine
- Keywords
- HSIL, CIN, HPV, HPV vaccination, gardasil, HIV, cervical dysplasia, LEEP, cervical cancer
- Medical subject headings
- Uterine Cervical Dysplasia, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Papillomavirus vaccineBiological
Also called qHPV vaccine
The participants receive the qHPV vaccine at entry, week 4 and week 26
| Study group | Role | What they receive |
|---|---|---|
| Human Papillomavirus vaccine | Experimental | Participants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26. Receives: Biological: Human Papillomavirus vaccine |
| Saline placebo | Placebo comparator | The participants receive saline placebo at entry, week 4 and week 26. Receives: Biological: Human Papillomavirus vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cervical HSIL
For this trial, the primary endpoint is high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells suggestive of HSIL found on cervical cytology, or HSIL found on cervical biopsy specimens at either the week 26 or week 52 visit.
Measured: up to 52 weeks
Secondary outcomes (1)
Cervical Cytology
Cervical cytology abnormalities according to the Bethesda scale. The Bethesda scale classifies cytologic abnormalities. We have dichotomized the outcomes into high grade squamous intraepithelial lesions (HSIL)/atypical squamous cells suggestive of HSIL, or no evidence of intraepithelial lesions or malignancy (NILM)/atypical squamous cells of unknown significance (ASC-US)/low grade squamous intraepithelial lesions (LSIL). We report the number of women in each category.
Measured: Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2013 (estimated)
- Study start2 Sep 2014
- Primary completion30 Nov 2017
- Study completion1 Mar 2018
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 (1)Papers the sponsor has linked to this study.
- Other trials for Cervical High Grade Squamous Intraepithelial LesionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Cynthia S Firnhaber, University of Witwatersrand, South Africa
- Investigators
- Timothy J Wilkin, M.D. MPH, Study chair, Weill Medical College of Cornell UniversityCynthia Firnhaber, M.D., Study chair, University or Witswatersrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01928225
- Sponsor's protocol ID
- QHPV-RTC
- Status last verified
- Jun 2020
- First submitted
- 20 Aug 2013
- Last updated
- 24 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Firnhaber C, Swarts A, Jezile V, Mulongo M, Goeieman B, Williams S, Faesen M, Michelow P, Wilkin T. Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial. Clin Infect Dis. 2021 Oct 5;73(7):e2211-e2216. doi: 10.1093/cid/ciaa1456.
PubMed 32975556
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled Trial of Pre-treatment HPV Vaccination on Outcomes to LEEP Treatment of Cervical High Grade Squamous Intraepithelial Lesions in HIV-infected Women.
- ClinicalTrials.gov ID
- NCT01928225
- Acronym / sponsor ID
- QHPV-RTC
- Keywords
- HSIL, CIN, HPV, HPV vaccination, gardasil, HIV, cervical dysplasia, LEEP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 2 Sep 2014 (actual)
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 1 Mar 2018 (actual)
- First posted
- 23 Aug 2013 (estimated)
- Results
- Posted 24 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cervical cancer occurs commonly in HIV-infected women in South Africa. These women have poor response to treatment of cervical cancer precursors. This study will test whether giving the quadrivalent vaccine to women prior to surgical treatment of the cervical cancer precursor will improve outcomes. We hypothesize that pre-treatment HPV vaccine will result in a reduced occurrence or cervical cancer precursors in follow-up.
Detailed description
This is a single-center, randomized, double-blinded, placebo-controlled, phase II trial of the quadrivalent human papillomavirus vaccine (qHPV) in HIV-infected women to prevent occurrence of cervical HSIL after LEEP/LLETZ. Participants will undergo colposcopy with directed biopsies, cervical cytology, and stored HPV testing prior to vaccination. Participants will be randomized to the quadrivalent vaccine or saline placebo to be given at entry, week 4, and week 26. Women will have LEEP treatment at week 4. Participants will be seen in follow-up for cervical cytology, colposcopy with directed biopsies at weeks 26 and 52, and stored HPV specimens. Treatment assignment will be unblinded after study follow-up is completed for the last study participant. Women aged 45 or less randomized to placebo will be offered open label HPV vaccine after the study is concluded..
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Human Papillomavirus vaccine | Experimental | Biological: Human Papillomavirus vaccineParticipants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26. |
| Saline placebo | Placebo comparator | Biological: Human Papillomavirus vaccineThe participants receive saline placebo at entry, week 4 and week 26. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HIV infection
- Women aged ≥ 18 years.
- Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3)
- For participants of reproductive potential, negative serum or urine pregnancy test
- All study participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) during study participation (from the time of study entry until week 52).
Key exclusion criteria (11 listed)
- History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer
- Prior hysterectomy
- Cervical cryotherapy or LEEP/LEETZ within one year of entry.
- Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer
- Prior receipt of one or more doses of an HPV vaccine.
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 |
|---|---|---|
| Human Papillomavirus vaccineAlso: qHPV vaccineThe participants receive the qHPV vaccine at entry, week 4 and week 26 | Biological | Human Papillomavirus vaccine, Saline placebo |
Primary outcome
Cervical HSIL
Time frame: up to 52 weeks
For this trial, the primary endpoint is high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells suggestive of HSIL found on cervical cytology, or HSIL found on cervical biopsy specimens at either the week 26 or week 52 visit.
1 secondary outcome
Cervical Cytology
Time frame: Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32975556Firnhaber C, Swarts A, Jezile V, Mulongo M, Goeieman B, Williams S, Faesen M, Michelow P, Wilkin T. Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial. Clin Infect Dis. 2021 Oct 5;73(7):e2211-e2216. doi: 10.1093/cid/ciaa1456.
- Individual participant dataSharing planned: Undecided
Related trials for Cervical High Grade Squamous Intraepithelial Lesion
Active, not recruitingObservational study
Predictive Biomarkers for Precision Management of Pre-cancerous Cervical Neoplasia
HSIL, High Grade Squamous Intraepithelial Lesion, DNA Methylation
Recruiting
Multicenter Prospective Non-randomized Controlled Study of Ella Photodynamic Therapy for Cervical HSIL/CIN2
HSIL, High Grade Squamous Intraepithelial Lesion, CIN 2
Active, not recruitingPhase 2
Pembrolizumab for the Treatment of Cervical Intraepithelial Neoplasia
Cervical Intraepithelial Neoplasia, Cervical Squamous Cell Carcinoma In Situ
Active, not recruiting
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico
AIDS-Related Anal Carcinoma, AIDS-Related Cervical Carcinoma
Active, not recruiting
Dual-Modality Immunotherapy for HPV Clearance (DUAL-HPV)
Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia (CIN)
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.
Timothy J Wilkin, M.D. MPH study chair
Weill Medical College of Cornell University
Cynthia Firnhaber, M.D. study chair
University or Witswatersrand
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Human Papillomavirus vaccine in people with Cervical High Grade Squamous Intraepithelial Lesion, run by University of Witwatersrand, South Africa.
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 5 inclusion and 11 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: finished, as of the sponsor's last update on 24 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Jun 2020). 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?
Cervical HSIL (time frame: up to 52 weeks). 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 NCT01928225, which also lists 1 linked publication.
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 24 Jun 2020.