Study of Pomalidomide in Anal Cancer Precursors

Study Overview
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Brief Summary
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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.

Official Title
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Study of Pomalidomide in Anal Cancer Precursors (SPACE): a Phase 2 Study of Immunomodulation in People With Persistent HPV-associated High Grade Squamous Intraepithelial Lesions

Conditions
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High Grade Squamous Intra-epithelial Lesion (HSIL)

Intervention / Treatment
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* Drug: Pomalidomide 2 MG Oral Capsule [Pomalyst]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). No history of thromboembolic disease No evidence of anal cancer or Superficially Invasive Squamous Cell Carcinoma of the Anus (SISCCA) Willingness to use appropriate contraception (including refraining from sperm donation) Age 18 years or older Provision of written informed consent In addition, for subjects with HIV: Adherence to a stable suppressive antiretroviral therapy (ART) regimen, unchanged for at least two months CD4+ count ≥ 200 cells/µl HIV viral load < 200 copies/mL for at least six months Exclusion Criteria: Absolute neutrophil count (ANC) <1000 cells/μL Haemoglobin <10.0 g/dL Platelet count <75,000 cells/μL Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > three times upper limit of normal Calculated or measured creatinine clearance (CLCr) ≤ 50 mL/min (calculated by Cockcroft-Gault formula) 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 Current pregnancy or breastfeeding 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, phase 2 trial, single-arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomalidomide group<br>Open label - all participants will receive pomalidomide 2mg orally once a day for 6 cycles (21 days on treatment and a 7 day rest period constitutes a cycle). | Drug: Pomalidomide 2 MG Oral Capsule [Pomalyst]<br>* 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.<br>* Other names: Pomalyst;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological High Grade Squamous Intraepithelial Lesions (HSIL) clearance at 6 months of therapy | Histological high grade squamous intra-epithelial lesion clearance | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of grade 3 and 4 adverse events and therapy delays (tolerability) | incidence of grade 3 and 4 adverse events and therapy delays (tolerability) | 6 months | 
| number of subjects completing of full six month course | number of subjects completing of full six month course (feasibility of polidamide in this setting) | 6 months | 
| effect of pomalidomide on self-reported health related quality of life and cancer anxiety during and after therapy | individual patient change in quality of life questionnaire (SF12) from baseline to mid therapy and end therapy | 6 months |