Cervical Intraepithelial NeoplasiaPhase 3HOPE9NCT03848039
Impact on Disease Relapse of HPV Vaccination in Women Treated With LEEP for Cervical Intraepithelial Neoplasia. HOPE9
A Phase 3 study testing Gardasil-9 in people with Cervical Intraepithelial Neoplasia, run by Alessandro Ghelardi.
Trial summary
This study evaluates the impact on disease relapse of presurgical 9-valent HPV vaccination versus placebo vaccination in women treated with LEEP (loop electrosurgical excision procedure) for CIN2+ (high grade cervical intraepithelial neoplasia) and initially invasive cervical cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia
- What is being tested?
- Gardasil-9
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,220 participants
- Where
- No sites listed yet
- Study dates
- Dec 2020to May 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Patients aged ≥ 18 and ecog performance status ≤ 1
- Patients with a diagnosis of high-grade cervical intraepithelial neoplasia or initially invasive cervical cancer (histological results ≥ CIN2 + and ≤ Ia1 according to the FIGO staging of cervical cancer)
- No fever at the time of vaccination
- No previous HPV vaccination
- Ability to understand and write Italian
- Signed informed and privacy consent
Who cannot join
- Patients enrolled in other clinical studies
- History of allergic reaction or serious adverse events to previous vaccinations
- Positive pregnancy test at the time of vaccination
- Patient in treatment with immunosuppressive therapy
- Subjects who received immunoglobulins or blood products in 3 months prior to vaccination.
- Thrombocytopenia or any other clotting disorder that may lead to bleeding as a result of intramuscular administration
- Clinical criteria contraindicating the surgical act of conization
- ECOG performance status ≥2
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Randomised, Double-Blind, Placebo-Controlled, Phase III Study to Investigate the Efficacy of Presurgical 9-valent HPV Vaccination in Women Treated With LEEP for CIN 2+ and Initially Invasive Cervical Cancer.
This study evaluates the impact on disease relapse of presurgical 9-valent HPV vaccination versus placebo vaccination in women treated with LEEP (loop electrosurgical excision procedure) for CIN2+ (high grade cervical intraepithelial neoplasia) and initially invasive cervical cancer.
Read the detailed description
Rationale:
In 2006 HPV vaccination was licensed for primary prevention programs worldwide. Only a few years after, several studies have raised new scenarios about HPV related diseases with strong implications on clinical management in adult women. Some findings from retrospective data have shown a significant effect of HPV vaccine on women and men treated for HPV pathologies. Although vaccination is not effective in patients with prevalent HPV infection, some studies have suggested that HPV vaccine could influence the incidence of the disease relapse after a surgical treatment. Reduction in disease recurrence after surgical treatment in vaccinated patients comes from gastroenterological, gynecological and dermatological evidences concerning both benign lesions (warts) and precancerous lesions.
If vaccination reduces recurrence rates by 80%, according to our previous pilot study data, peri-surgical HPV vaccination will be a strong effective clinical intervention, very likely to be introduced into standard high grade cervical intraepithelial neoplasia management.
Objective:
The primary objective of the current study is to assess the efficacy of 9-valent HPV vaccination in preventing recurrence of CIN2+ in participants treated for high-grade CIN.
Study population: participants treated for CIN2+ with LEEP technique. Study design: A multicenter, randomised, double-blind clinical trial in 9 hospitals in Italy.
Intervention: Participants will be randomized in a 1:1 ratio to receive presurgical 9-valent HPV vaccination (Gardasil-9 ®) or placebo at months 0 (at pre-surgical enrollment time), at 2 months (the same day of surgical treatment) and 6 moths (during the first follow-up visit after surgery). The randomization list will be generated before the start of the study.
Main study parameters/endpoints:
Primary end point will be the cumulative recurrence of CIN2+ after conization, as assessed by biopsies taken of suspect lesions, histologically confirmed for high grade cervical intraepithelial neoplasia recurrence.
Secondary outcome measures are cumulative incidence/persistence of HPV infection after the surgical treatment, causative HPV type in recurrent CIN lesions, as assessed by HPV test and PCR (polymerase chain reaction).
The total sample size is estimated to be 1220 patients based on an expected recurrence rate of less than 6% within 5 years. Statistical analysis will be based on the intention-to-treat protocol. Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 0,05 two-sided significance level.
Follow-up schedule (FUP) will be the same in both arms, with a FUP evaluation every 6 months in the first year followed by an annual evaluation for a total of 5 years. FUP visit will include HPV test, Pap-test and colposcopy. HPV test will be collected in order to evaluate the HPV infection clearance rate in both arms. HPV test will be part of all the follow-up visits allowing to study the natural history of HPV infection after the surgical treatment.
- Conditions
- Cervical Intraepithelial Neoplasia
- Being tested
- Gardasil-9, Placebo
- Keywords
- Cervical Cancer, cervical intraepithelial neoplasia, Papillomavirus Vaccines
- 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.
Gardasil-9Biological
Also called 9-valent HPV vaccine, Vaccine against HPV-6, 11, 16, 18, 31, 33, 45, 52, 58
administration by intramuscular injection of the 9-valent HPV vaccine according to a 3-dose vaccination schedule (0, 2, 6 months).
PlaceboDrug
Also called Sterile Water for Injection Ph. Eur.
administration by intramuscular injection of the placebo according to vaccination schedule of the 9-valent HPV vaccine (0, 2, 6 months)
| Study group | Role | What they receive |
|---|---|---|
| Gardasil-9 | Experimental | Intramuscular Gardasil-9 vaccination at 0, 2 and 6 months. Receives: Biological: Gardasil-9 |
| Placebo | Placebo comparator | Placebo injection at 0, 2 and 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluation of disease recurrence reduction (cervical intraepithelial neoplasia up to microinvasive cancer of the cervix)
evaluation of disease recurrence reduction (cervical intraepithelial neoplasia up to microinvasive cancer of the cervix) by comparing the number of recurrences in the two arms of the study
Measured: 5 years after surgical treatment
Secondary outcomes (2)
impact of the vaccine on prevalent post-surgery infections
Analysis of the impact of the vaccine on prevalent post-surgery infections by comparing the prevalence of persistent HPV infections (duration greater than 12 months after surgery) in the two arms.
Measured: 5 years after surgical treatment
impact of the vaccine in the post-surgical surveillance times, comparison of viral wash-out times (negativity of the HPV test), times of negativization of the pap test and of the colposcopic picture in the post-operative period
Analysis of the impact of the vaccine in the post-surgical surveillance times, comparison of the viral wash-out times (negativity of the HPV test), times of negativization of the pap test and of the colposcopic picture in the post-operative period: comparison of the times of negativization overexposed in the two arms.
Measured: 5 years after surgical treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study startDec 2020 (estimated)
- Primary completionDec 2022 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical Intraepithelial NeoplasiaStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alessandro Ghelardi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alessandro Ghelardi, Azienda USL Toscana Nord Ovest
- Investigators
- Alessandro Ghelardi, MD, Principal investigator, Az. USL Toscana Nord Ovest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03848039
- Sponsor's protocol ID
- HOPE9 STUDY
- Other IDs
- 2018-003507-19, 2018
- Acronym
- HOPE9
- Status last verified
- Nov 2020
- First submitted
- 19 Feb 2019
- Last updated
- 5 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-Blind, Placebo-Controlled, Phase III Study to Investigate the Efficacy of Presurgical 9-valent HPV Vaccination in Women Treated With LEEP for CIN 2+ and Initially Invasive Cervical Cancer.
- ClinicalTrials.gov ID
- NCT03848039
- Acronym / sponsor ID
- HOPE9 / HOPE9 STUDY
- Conditions
- Cervical Intraepithelial Neoplasia
- Keywords
- Cervical Cancer, cervical intraepithelial neoplasia, Papillomavirus Vaccines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,220 participants (estimated)
- Lead sponsor
- Alessandro GhelardiUniversity, hospital or other
- Study start
- Dec 2020 (estimated)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 20 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the impact on disease relapse of presurgical 9-valent HPV vaccination versus placebo vaccination in women treated with LEEP (loop electrosurgical excision procedure) for CIN2+ (high grade cervical intraepithelial neoplasia) and initially invasive cervical cancer.
Detailed description
Rationale:
In 2006 HPV vaccination was licensed for primary prevention programs worldwide. Only a few years after, several studies have raised new scenarios about HPV related diseases with strong implications on clinical management in adult women. Some findings from retrospective data have shown a significant effect of HPV vaccine on women and men treated for HPV pathologies. Although vaccination is not effective in patients with prevalent HPV infection, some studies have suggested that HPV vaccine could influence the incidence of the disease relapse after a surgical treatment. Reduction in disease recurrence after surgical treatment in vaccinated patients comes from gastroenterological, gynecological and dermatological evidences concerning both benign lesions (warts) and precancerous lesions.
If vaccination reduces recurrence rates by 80%, according to our previous pilot study data, peri-surgical HPV vaccination will be a strong effective clinical intervention, very likely to be introduced into standard high grade cervical intraepithelial neoplasia management.
Objective:
The primary objective of the current study is to assess the efficacy of 9-valent HPV vaccination in preventing recurrence of CIN2+ in participants treated for high-grade CIN.
Study population: participants treated for CIN2+ with LEEP technique. Study design: A multicenter, randomised, double-blind clinical trial in 9 hospitals in Italy.
Intervention: Participants will be randomized in a 1:1 ratio to receive presurgical 9-valent HPV vaccination (Gardasil-9 ®) or placebo at months 0 (at pre-surgical enrollment time), at 2 months (the same day of surgical treatment) and 6 moths (during the first follow-up visit after surgery). The randomization list will be generated before the start of the study.
Main study parameters/endpoints:
Primary end point will be the cumulative recurrence of CIN2+ after conization, as assessed by biopsies taken of suspect lesions, histologically confirmed for high grade cervical intraepithelial neoplasia recurrence.
Secondary outcome measures are cumulative incidence/persistence of HPV infection after the surgical treatment, causative HPV type in recurrent CIN lesions, as assessed by HPV test and PCR (polymerase chain reaction).
The total sample size is estimated to be 1220 patients based on an expected recurrence rate of less than 6% within 5 years. Statistical analysis will be based on the intention-to-treat protocol. Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 0,05 two-sided significance level.
Follow-up schedule (FUP) will be the same in both arms, with a FUP evaluation every 6 months in the first year followed by an annual evaluation for a total of 5 years. FUP visit will include HPV test, Pap-test and colposcopy. HPV test will be collected in order to evaluate the HPV infection clearance rate in both arms. HPV test will be part of all the follow-up visits allowing to study the natural history of HPV infection after the surgical treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gardasil-9 | Experimental | Biological: Gardasil-9Intramuscular Gardasil-9 vaccination at 0, 2 and 6 months. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo injection at 0, 2 and 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients aged ≥ 18 and ecog performance status ≤ 1
- Patients with a diagnosis of high-grade cervical intraepithelial neoplasia or initially invasive cervical cancer (histological results ≥ CIN2 + and ≤ Ia1 according to the FIGO staging of cervical cancer)
- No fever at the time of vaccination
- No previous HPV vaccination
- Ability to understand and write Italian
Key exclusion criteria (8 listed)
- Patients enrolled in other clinical studies
- History of allergic reaction or serious adverse events to previous vaccinations
- Positive pregnancy test at the time of vaccination
- Patient in treatment with immunosuppressive therapy
- Subjects who received immunoglobulins or blood products in 3 months prior to 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 |
|---|---|---|
| Gardasil-9Also: 9-valent HPV vaccine, Vaccine against HPV-6, 11, 16, 18, 31, 33, 45, 52, 58administration by intramuscular injection of the 9-valent HPV vaccine according to a 3-dose vaccination schedule (0, 2, 6 months). | Biological | Gardasil-9 |
| PlaceboAlso: Sterile Water for Injection Ph. Eur.administration by intramuscular injection of the placebo according to vaccination schedule of the 9-valent HPV vaccine (0, 2, 6 months) | Drug | Placebo |
Primary outcome
evaluation of disease recurrence reduction (cervical intraepithelial neoplasia up to microinvasive cancer of the cervix)
Time frame: 5 years after surgical treatment
evaluation of disease recurrence reduction (cervical intraepithelial neoplasia up to microinvasive cancer of the cervix) by comparing the number of recurrences in the two arms of the study
2 secondary outcomes
impact of the vaccine on prevalent post-surgery infections
Time frame: 5 years after surgical treatment
impact of the vaccine in the post-surgical surveillance times, comparison of viral wash-out times (negativity of the HPV test), times of negativization of the pap test and of the colposcopic picture in the post-operative period
Time frame: 5 years after surgical treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Alessandro Ghelardi, MD principal investigator
Az. USL Toscana Nord Ovest
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gardasil-9 in people with Cervical Intraepithelial Neoplasia, run by Alessandro Ghelardi.
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 6 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: opening soon, as of the sponsor's last update on 5 Nov 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alessandro Ghelardi, MD (+39 0585 6571, alessandro.ghelardi@uslnordovest.toscana.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
evaluation of disease recurrence reduction (cervical intraepithelial neoplasia up to microinvasive cancer of the cervix) (time frame: 5 years after surgical treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2020.