Impact on Disease Relapse of HPV Vaccination in Women Treated With LEEP for Cervical Intraepithelial Neoplasia. HOPE9

NCT ID: NCT03848039

Last Updated: 2020-11-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2028-05-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Gardasil-9

Intramuscular Gardasil-9 vaccination at 0, 2 and 6 months.

Group Type: EXPERIMENTAL

Gardasil-9

Intervention Type: BIOLOGICAL

administration by intramuscular injection of the 9-valent HPV vaccine according to a 3-dose vaccination schedule (0, 2, 6 months).

Placebo

Placebo injection at 0, 2 and 6 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

administration by intramuscular injection of the placebo according to vaccination schedule of the 9-valent HPV vaccine (0, 2, 6 months)

Interventions

Gardasil-9

administration by intramuscular injection of the 9-valent HPV vaccine according to a 3-dose vaccination schedule (0, 2, 6 months).

Intervention Type: BIOLOGICAL

Placebo

administration by intramuscular injection of the placebo according to vaccination schedule of the 9-valent HPV vaccine (0, 2, 6 months)

Intervention Type: DRUG

Other Intervention Names

9-valent HPV vaccine; Vaccine against HPV-6, 11, 16, 18, 31, 33, 45, 52, 58; Sterile Water for Injection Ph. Eur.

Eligibility Criteria

Inclusion Criteria

1. Patients aged ≥ 18 and ecog performance status ≤ 1

2. 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)

3. No fever at the time of vaccination

4. No previous HPV vaccination

5. Ability to understand and write Italian

6. Signed informed and privacy consent

Exclusion Criteria

1. Patients enrolled in other clinical studies

2. History of allergic reaction or serious adverse events to previous vaccinations

3. Positive pregnancy test at the time of vaccination

4. Patient in treatment with immunosuppressive therapy

5. Subjects who received immunoglobulins or blood products in 3 months prior to vaccination.

6. Thrombocytopenia or any other clotting disorder that may lead to bleeding as a result of intramuscular administration

7. Clinical criteria contraindicating the surgical act of conization

8. ECOG performance status ≥2

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Alessandro Ghelardi

OTHER

Sponsor Role: lead

Responsible Party

Alessandro Ghelardi

Principal Investigator, Department of Obstetrics and Gynaecology Azienda USL Toscana Nord Ovest, Presidio Ospedaliero delle Apuane (MS)- Italy

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alessandro Ghelardi, MD

Role: PRINCIPAL_INVESTIGATOR

Az. USL Toscana Nord Ovest

Central Contacts

Alessandro Ghelardi, MD

Role: CONTACT

alessandro.ghelardi@uslnordovest.toscana.it

+39 0585 6571

Paola Bay, MD

Role: CONTACT

paola.bay@uslnordovest.toscana.it

+39 0585 6571

Other Identifiers

2018-003507-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HOPE9 STUDY

Identifier Type: -

Identifier Source: org_study_id