Anal Cancer Precursors High Grade Anal Intraepithelial Neoplasia Precursor anal cancer
Conditions
Interventions
For this amendment, we would like to use the remaining inclusions of the TREMA study, to use the intra-anal biopsies for the creation of organoids. 
Like the TREMA study, patients with intra-anal HGAIN who will undergo treatment with electrocautherisation. Before treatment, 2 intra-anal biopsies will be taken.
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Study group (N=200) - HIV+ patients of at least 18 years of age that are cisgender men, transgender men or transgender women and who have sex with men (further referred to as HIV+ MSM); - histopathological confirmed HGAIN (>=1 lesion); - satisfactory HRA at baseline, i.e. visualisation of entire transformation zone with biopsies of all lesions; Substudy HIV-positive group (N=20): - >18 years of age - Compliance to ART, undetectable viral load since at least 1 year - A low nadir CD4 cell count (<200 cell/µl) - Histopathologically confirmed HGAIN (>=1 lesion); - Satisfactory HRA at baseline, i.e. visualisation of entire transformation zone with biopsies of all lesions; Substudy HIV-negative group (N=20) - >18 years of age - Histopathologically confirmed HGAIN (>=1 lesion); - Satisfactory HRA at baseline, i.e. visualisation of entire transformation zone with biopsies of all lesions;In this amendment we will increase the study group by 50 patients (in total N=250) due to drop out during study inclusion.
Exclusion criteria
Exclusion criteria: Study group: - HGAIN covering more than 50% of the circumference of the anal canal (progression to cancer of these patients is estimated as high and therefore withholding treatment would be unethical); - clinical suspicion for anal cancer, defined as palpable abnormalities at DARE and suspicion of invasion at MRI; - histopathological diagnosis of anal cancer; - history of anal cancer; - previous HPV vaccination (including participants of the VACCAIN-T and VACCAIN-P trial); - concomitant cancer; - insufficient Dutch or English language skills. Substudy group (N=40): - Clinical suspicion for anal cancer, defined as palpable abnormalities at DARE and suspicion of invasion at MRI; - Histopathological diagnosis of anal cancer; - History of anal cancer; - Previous HPV vaccination (including participants of the VACCAIN-T and VACCAIN-P trial); - Known active chronic infection such as hepatitis B or C - Diabetes mellitus - Insufficient Dutch or English language skills. - Presence of any diseases affecting the anal mucosa (fistulas, rhagades, eczema). - Signs of current STI.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • The primary endpoint is the regression / non-regression dichotomy of each individual HGAIN lesion at baseline. • The primary endpoint is based on the histological outcome of the 24-months follow-up anal biopsies from each individual HGAIN lesion. • The histological outcome is based on the LGAIN/HGAIN dichotomy according to the LAST criteria. • To follow-up each individual HGAIN lesion, its location is recorded along 8 segments (octants) along the circular transformation zone in the anal canal. • Regression is defined as any biopsy-proven LGAIN, or no AIN lesion in the octant of an individual HGAIN lesion previously seen at baseline, or in one of the adjacent octants. • If no clinical lesion is visible upon HRA at 24 months, a biopsy is obtained at random form the octant where the individual HGAIN lesion was previously seen at baseline. • HGAIN non-regression is defined as any biopsy-proven HGAIN lesion or anal cancer in the octant of an individual HGAIN lesion previously seen at baseline, or in one of the adjacent octants. For the substudy, endpoints are: 1. To determine the frequency and phenotype of CXCR3+ TRMs in AIN lesions of HIV-positive and HIV-negative individuals. 2. To identify HIV-specific altered immune pathways associated with CXCR3 expression, tumor progression, and/or aberrant immune responses to HPV at the single-cell level. 3. To validate the presence and functional relevance of cTRMs in HPV by characterizing their clone sequence and phenotype in pre-cancerous lesions. 4. To identify hot-spots of intensive HPV antiviral defense and cell-cell interaction in the pre-cancerous lesion at the sub-compartmental level using imaging and transcriptomic approaches. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are: • The histological outcome of each individual HGAIN lesion at the 6-, 12-, and 18-month follow-up visits. • The clinical outcome of each individual HGAIN lesion at the 6-, 12-, 18-, and 24-month follow-up visits, defined as a change in the size measured by the number of octants of the anal surface affected • Overall HGAIN disease: the clinical outcome of all HGAIN lesions combined at the 6-, 12, 18-, and 24-month follow-up visits, defined as a change in the size of any HGAIN lesion, measured by the number of octants of the anal surface affected, including incident HGAIN lesions during, and in between follow-up visits. • Overall HGAIN disease: the histological outcome of all HGAIN lesions combined at the 6-, 12-, 18, and 24-month follow-up visits. • HRQoL of the study population compared to the control population at baseline, the 6- and the 24-month follow-up visit. For the substudy, endpoints are: 1. To determine the frequency and phenotype of CXCR3+ TRMs in AIN lesions of HIV-positive and HIV-negative individuals. 2. To identify HIV-specific altered immune pathways associated with CXCR3 expression, tumor progression, and/or aberrant immune responses to HPV at the single-cell level. 3. To validate the presence and functional relevance of cTRMs in HPV by characterizing their clone sequence and phenotype in pre-cancerous lesions. 4. To identify hot-spots of intensive HPV antiviral defense and cell-cell interaction in the pre-cancerous lesion at the sub-compartmental level using imaging and transcriptomic approaches. | — |
Countries
Netherlands
Contacts
Public ContactW.C. Kan
Amsterdam UMC
Outcome results
None listed