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Intramuscular Saline 0.9% vaccination at 0, 2 and 6 months

Intramuscular Gardasil vaccination at 0, 2 and 6 months.

Gardasil

Placebo

Jan M Prins, prof, MD, infectiologist

Henry JC de Vries, prof, MD, dermatologist

This study evaluates vaccination with the quadrivalent HPV vaccine (Gardasil) versus placebo vaccination on prevention of high grade AIN recurrence in HIV-positive MSM (men who have sex with men) who were successfully treated for high grade AIN.

Rationale: Since the introduction of combination antiretroviral therapy (cART), human immunodeficiency virus (HIV)-related morbidity and mortality have considerably decreased. However, as a result of the significantly prolonged life span, new causes of morbidity and mortality have become evident. In particular, anal cancer incidence has increased dramatically in HIV-positive men. Like cervical cancer, anal cancer is causally linked to infections with high-risk papillomaviruses, and is preceded by precursor lesions: anal intraepithelial neoplasia (AIN). Over 90% of HIV-positive MSM (men who have sex with men) have persisting anal HPV (human papilloma virus) infection, and high-grade (HG) AIN is present in 30% of all HIV+ MSM.

As in cervical intraepithelial neoplasia, early diagnosis and treatment of AIN have been advocated to prevent malignancy. Electrocoagulation/ cauterization is standard of care for intra-anal AIN, but after treatment, recurrence of lesions occurs in approx. 50% of cases. This is a major problem in an effective screening program for AIN.

In a nonconcurrent, non-blinded cohort study qHPV (quadrivalent human papilloma virus) vaccination significantly (HR 0.50) reduced HG AIN recurrence among MSM successfully treated for AIN. This is in accordance with findings in women treated for cervical intraepithelial neoplasia. Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease.

Therefore, a strategy that is worth investigating is vaccination with the qHPV vaccine to prevent recurrences in HIV+ MSM who were successfully treated for HG AIN.

Objective: The primary objective of the current study is to assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV+ MSM with CD4 counts \>350 x 10E6/l who were successfully treated for high-grade intra-anal AIN in the past year.

Study population: HIV-positive MSM with a CD4 count \> 350 cells/ul and intra-anal high-grade AIN (grade 2-3) that was successfully treated in the past year with conventional cauterization, cryotherapy, or other forms of local treatment.

Study design: A multicenter, randomised, double-blind clinical trial in four hospitals in the Netherlands.

Intervention: Patients are randomised for vaccination with the quadrivalent HPV vaccine (Gardasil ®) or vaccination with a matching placebo at months 0, 2 and 6.

Randomisation will be stratified for complete response versus partial response (from HG AIN to low-grade (LG) AIN) of the initial HG AIN lesion, for treatment less than 6 months ago versus treatment 6 months and longer ago, and for AMC versus other hospitals.

Main study parameters/endpoints: Screening for AIN will be performed by high-resolution anoscopy (HRA), at inclusion (first vaccination) and at last vaccination (6 months), and repeated at 6 and 12 months after the last vaccination. Safety Monitoring for adverse events and injection-site reactions will be performed one week after each vaccination and thereafter every 6 months for a total of 12 months of follow-up.

Primary end point will be the cumulative recurrence of HG AIN at 12 months after the last vaccination, as assessed by HRA (High-Resolution Anoscopy), with biopsies taken of suspect lesions.

Secondary outcome measures are toxicity/ safety, recurrence of HG AIN at last vaccination and 6 months afterwards, cumulative occurrence of LG AIN at 12 months after the last vaccination, cumulative occurrence of anogenital warts at 12 months after the last vaccination, causative HPV type in recurrent AIN lesions, as assessed by LCM (Laser Capture Microdissection)/ PCR (polymerase chain reaction), and HPV type-specific antibody response.

The total sample size is estimated to be 125 patients based on an expected recurrence rate of 50% within 12 months. Statistical analysis will be based on the intention-to-treat principle. Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 0,05 two-sided significance level.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

HIV+ MSM who were successfully treated for HG AIN are still at a 50% risk for recurrences, with additional treatment sessions needed, and an ongoing risk for malignant degeneration of lesions.

Costs of 3 vaccinations are approx. € 400, but if vaccination reduces recurrence rates by 50%, this will be a highly cost-effective intervention, very likely to be introduced into regular care.

For the study, patients will be vaccinated 3 times with the quadrivalent vaccine Gardasil ® or placebo, and will undergo two extra HRAs. Clinical trial data show that the most common adverse events of Gardasil ® were mild or moderate, so few risks are associated with study participation.

HPV (Human Papilloma Virus) Vaccination After Treatment of Anal Intraepithelial Neoplasia (AIN)

Quadrivalent HPV Vaccination After Effective Treatment of Anal Intraepithelial Neoplasia in HIV+ Men

One week after each vaccination and during all follow up visits the most common adverse events of Gardasil and other eventually occuring complaints will be evaluated by history taking. Adverse events will be graded according to the CTCAE v4 (Common Terminology Criteria for Adverse Events), which grades events on a scale of 1 to 5, with higher grades indicating greater severity.

The patients with LG AIN at inclusion are excluded from this analysis.

Evaluated by physical examination and history taking.

Prof. Jan Prins

Professor. dr. J.M. Prins

Skin and Connective Tissue Diseases

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Granulocytopenia

The first level prophylactic use of PEG-rhG-CSF. The Prophylactic use of PEG-rhG-CSF in all cycles of chemotherapy.

The second level prophylactic use of PEG-rhG-CSF. The Prophylactic use of PEG-rhG-CSF in the next cycle until FN or 4 grade neutropenia happened.

6mg (≥45kg) or 3mg (\<45kg) i.h. once 24h after chemotherapy in all cycles of chemotherapy

PEGCSF first level prophylactic use

6mg (≥45kg) or 3mg (\<45kg) i.h. once 24h after chemotherapy in next cycle if FN or 4 grade neutropenia happened

PEGCSF second level prophylactic use

Hongjian Yang, MD

Haiyan Xu, MD

This clinical study is a multiple center, registering and real-world conditional research. The breast cancer patients planning for chemotherapy evaluated with medium-high risk of febrile neutropenia (FN) are recruited, receiving the first level prophylactic use of PEG-rhG-CSF or the second level prophylactic use of PEG-rhG-CSF in at least two cycles of chemotherapy according to real-world clinical judgement and choice by physicians in local cancer center. Comparing real conditional-FN rate, FN-caused hospitalization rate and antibiotic use rate, direct/indirect medical cost.

The breast cancer patients planning for neo-adjuvant/adjuvant chemotherapy evaluated with medium-high risk of febrile neutropenia (FN) according to NCCN and ASCO guideline are recruited, receiving the first level prophylactic use of PEG-rhG-CSF or the second level prophylactic use of PEG-rhG-CSF according to real-world clinical judgement and choice by physicians in local cancer center for at least two cycles of chemotherapy. The primary outcome is FN rate, the second outcomes are rate of 3-4 grade decrease of ANC, FN-caused hospitalization, FN-caused antibiotic use rate, rate of reduction of chemotherapy dose, delay of chemotherapy, safety and pharmacoeconomics.

Prophylactic Use of PEG-rhG-CSF in Medium-high Risk of FN in Chemotherapy of Breast Cancer

The Effect, Safety and Pharmacoeconomics of First or Second Level-prophylactic Use of PEG-rhG-CSF in Breast Cancer Patients With Medium-high Risk of Febrile Neutropenia During Chemotherapy

rate of febrile neutropenia during all cycles of chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
HPV (Human Papilloma Virus) Vaccination After Treatment of Anal Intraepithelial Neoplasia (AIN)	NCT02087384	AIN HIV	Gardasil Placebo	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Prophylactic Use of PEG-rhG-CSF in Medium-high Risk of FN in Chemotherapy of Breast Cancer	NCT03618810	Febrile Neutrop...	PEGCSF first le... PEGCSF second l...	13 Years - 70 Years	Zhejiang Cancer Hospital
Prophylactic Use of PEG-rhG-CSF in Medium-high Risk of FN in Chemotherapy of Breast Cancer	NCT03618810	Febrile Neutrop...	PEGCSF first le... PEGCSF second l...	13 Years - 70 Years	Zhejiang Cancer Hospital

Spots Global Cancer Trial Database for prophylactic

Every month we try and update this database with for prophylactic cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.