Study of Pomalidomide in Anal Cancer Precursors

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

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.

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