E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human papilloma virus (HPV) causes cervical cancer. HPV vaccination is highly effective in primary prevention. There is less known about a possible secondary effect in women already infected with HPV. Our study proposes to investigate this efficacy in women with precursors of cervical cancer. HPV vaccination after surgical treatment to evaluate the efficacy to prevent recurrent disease. |
Humaan papillomavirus (HPV) veroorzaakt baarmoederhalskanker. HPV-vaccinatie is zeer effectief in primaire preventie. Er is minder bekend over een mogelijk secundair effect bij vrouwen die al met HPV zijn geïnfecteerd. Onze studie stelt voor om deze werkzaamheid te onderzoeken bij vrouwen met precursoren van baarmoederhalskanker. HPV-vaccinatie na chirurgische behandeling om de werkzaamheid te evalueren om recidiverende ziekte te voorkomen. |
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E.1.1.1 | Medical condition in easily understood language |
Precursor lesions of cervical cancer are caused by HPV. Vaccination with HPV-vaccine after LEEP to prevent recurrent disease. |
Voorloopstadia van baarmoederhalskanker worden veroorzaakt door HPV. Vaccinatie met HPV-vaccin na een lisexcisie om recidiverende ziekte te voorkomen |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028986 |
E.1.2 | Term | Neoplasm cervix |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the efficacy of nonavalent HPV vaccination in women with a CIN lesion who will undergo or have undergone a LEEP in preventing recurrent CIN II-III after 24 months. |
Evalueren van de werkzaamheid van HPV-vaccinatie bij vrouwen met een CIN leasie die een LEEP zullen of hebben ondergaan op het gebeid van preventie van recidiverende CIN II-III na 24 maanden. |
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E.2.2 | Secondary objectives of the trial |
1 Recurrence of CIN I-II-III at 6 and 24 months 2 The effect of treatments on HPV DNA presence 3 Pap-smear results 4 Number of LEEP 5 Cost-effectiveness analysis 6 Quality of life 7 Side effects and adverse events |
1 recidief CIN I-II-III op 6 en 24 maanden 2 Het effect van behandelingen op aanwezigheid van HPV-DNA 3 Pap-uitstrijkjes resultaten 4 Aantal lisexcisie (LEEP) 5 Kosten-batenanalyse 6 Kwaliteit van leven 7 Bijwerkingen complicaties |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women 18 years or above Histologically proven CIN II or III Patients treated with LEEP |
Vrouwen van 18 jaar of ouder Histologisch bewezen CIN II of III Patiënten behandeld met LEEP |
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E.4 | Principal exclusion criteria |
Prior HPV vaccination (Micro-) invasive carcinoma Immune-compromised patients Pregnancy Prior treatment for CIN-lesions Insufficient understanding of the Dutch language Women allergic to vaccine components |
Voorafgaande HPV-vaccinatie (Micro-) invasief carcinoom Immuungecompromiteerde patiënten Zwangerschap Voorafgaande behandeling voor CIN-laesies Onvoldoende begrip van de Nederlandse taal Vrouwen allergisch voor vaccincomponenten |
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E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence of CIN II-III after 24 months |
Recidief CIN II-III na 24 maanden |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 months after primary treatment. Follow-up is in accordance with the current follow-up protocol for CIN lesions. A negative hr-HPV test combined with a smear test outcome ‘Pap1’ are considered as normal (absence of dysplasia). The only part where this study deviates from the guideline is at our end point. When Pap smear or HPV test at 24 months is abnormal, a colposcopy will be performed and biopsies taken for histologic results. We choose this strategy to ensure an objective primary outcome with minimal invasive procedures. |
24 maanden na primaire behandeling. De follow-up is in overeenstemming met het huidige follow-up-protocol voor CIN-laesies. Een negatieve hr-HPV-test in combinatie met de uitkomst van een uitstrijkje wordt 'Pap1' als normaal beschouwd (afwezigheid van dysplasie). Het enige deel waar dit onderzoek afwijkt van de richtlijn ligt op ons eindpunt. Wanneer Pap uitstrijkje of HPV-test op 24 maanden is abnormaal, een colposcopie zal worden uitgevoerd en biopten worden genomen voor histologische resultaten. We kiezen deze strategie om een objectieve primaire uitkomst te garanderen met minimaal invasieve procedures. |
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E.5.2 | Secondary end point(s) |
- Recurrence rate of CIN I-II-III after 6 and 24 months. - The effect of treatments on HPV DNA presence - PAP-smear results - Number of LEEP - Cost-effectiveness analysis - Quality of life - Side effects and adverse events |
1 recidief CIN I-II-III op 6 en 24 maanden 2 Het effect van behandelingen op aanwezigheid van HPV-DNA 3 Pap-uitstrijkjes resultaten 4 Aantal lisexcisie (LEEP) 5 Kosten-batenanalyse 6 Kwaliteit van leven 7 Bijwerkingen complicaties |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to the Dutch guideline, the standard follow-up after treatment is 6 months and 24 months. After 2 months the second vaccination, QoL and questionnaire on social economic costs (iPCQ). After 6 months the last vaccination: cytology and HPV typing and QoL questionnaire. After 24 months, last visit: cytology and HPV testing QoL questionnaire. |
Volgens de Nederlandse richtlijn is de standaard follow-up na behandeling 6 maanden en 24 maanden. Na 2 maanden de tweede vaccinatie, QoL en vragenlijst over maatschappelijke economische kosten (iPCQ). Na 6 maanden de laatste vaccinatie: cytologie en HPV-typering en QoL-vragenlijst. Na 24 maanden, laatste bezoek: cytologie en HPV testen QoL-vragenlijst. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 18 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |