High Grade Squamous Intra-epithelial Lesion (HSIL)
Conditions
Brief summary
This is a single centre open label phase II trial to determine the antitumor efficacy of the oral immunomodulatory agent pomalidomide in persistent human papillomavirus (HPV) -associated high grade squamous intra-epithelial lesions (HSIL) in patients with and without human immunodeficiency virus (HIV) infection.
Interventions
DRUGPomalidomide 2 MG Oral Capsule [Pomalyst]
Pomalidomide is an oral immunomodulatory derivative of thalidomide. Thalidomide and its derivatives are small molecules with broad effects on immune activation, including T-cell activation and responsiveness. Pomalidomide augments T cell responsiveness and proliferation by several mechanisms, many mediated by transcriptional regulation downstream of its primary target, cereblon. Effects include increased production of IL-2 and interferon-γ (IFN-γ), enhanced CD4+ and CD8+ T cell co-stimulation.
Sponsors
Kirby Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, phase 2 trial, single-arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Persistent high grade squamous intra-epithelial lesion (HSIL) which must meet all of the following criteria: i. Pathologically confirmed grade 2 or 3 AIN demonstrated by high resolution anoscopy with grade on each occasion re-confirmed at screening by nominated study pathologist from Douglas Hanly Moir (DHM) (pathology case review to be conducted prior to enrolment) ii. Lesion must have been visualised on at least three sequential occasions over at least 12 months, including the pre enrolment screening high resolution anoscopy (HRA). iii. Lesion must have persistent geographical characteristics consistent with a single lesion observed over time (as defined in the Manual of Operations). 2. No history of thromboembolic disease 3. No evidence of anal cancer or Superficially Invasive Squamous Cell Carcinoma of the Anus (SISCCA) 4. Willingness to use appropriate contraception (including refraining from sperm donation) 5. Age 18 years or older 6. Provision of written informed consent In addition, for subjects with HIV: 7. Adherence to a stable suppressive antiretroviral therapy (ART) regimen, unchanged for at least two months 8. CD4+ count ≥ 200 cells/µl 9. HIV viral load \< 200 copies/mL for at least six months
Exclusion criteria
1. Absolute neutrophil count (ANC) \<1000 cells/μL 2. Haemoglobin \<10.0 g/dL 3. Platelet count \<75,000 cells/μL 4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> three times upper limit of normal 5. Calculated or measured creatinine clearance (CLCr) ≤ 50 mL/min (calculated by Cockcroft-Gault formula) 6. Patients with significant cardiac dysfunction including congestive heart failure, NY Heart Association Class II; Myocardial infarction within 12 months of starting study; unstable of poorly controlled angina 7. Current pregnancy or breastfeeding 8. Any condition not already outlined above which, in the opinion of the clinical investigator, would place the subject at risk if they participated or would jeopardise adherence or follow up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histological High Grade Squamous Intraepithelial Lesions (HSIL) clearance at 6 months of therapy | 6 months | Histological high grade squamous intra-epithelial lesion clearance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| incidence of grade 3 and 4 adverse events and therapy delays (tolerability) | 6 months | incidence of grade 3 and 4 adverse events and therapy delays (tolerability) |
| number of subjects completing of full six month course | 6 months | number of subjects completing of full six month course (feasibility of polidamide in this setting) |
| effect of pomalidomide on self-reported health related quality of life and cancer anxiety during and after therapy | 6 months | individual patient change in quality of life questionnaire (SF12) from baseline to mid therapy and end therapy |
Countries
Australia
Outcome results
None listed