Anal High Grade Squamous Intraepithelial Lesion
Conditions
Keywords
HSIL/AIN 2-3, Curcumin, Cancer, Human Papillomavirus (HPV), HIV, Curcuminoids
Brief summary
The purpose of this study is to see if curcumin can reverse anal high-grade squamous intraepithelial lesions (aHSIL) (high-grade anal precancerous cells or high-grade abnormal cells) in people living with HIV to avoid current treatments such as ablation (destroying abnormal cells with heat or surgical excision (cutting out the abnormal cells)), which have potential short- and long-term side effects.
Detailed description
This proposal suggests conducting a Phase I clinical trial using a 3 + 3 dose escalation approach to assess the safety and determine the maximum tolerated dose of intra-anal curcumin in individuals with HIV who have anal high-grade squamous intraepithelial lesions (aHSIL/AIN 2-3). Currently, there is a significant need for non-surgical treatments for pre-malignant anal diseases in people with HIV, aiming to reduce risks and complications associated with existing surgical and topical interventions. Curcumin, a compound derived from turmeric, is known for its anti-inflammatory and anti-infectious properties. While previous research has shown its anticancer effects in oral doses, its bioavailability is limited, and intra-anal administration has not been studied in humans. This trial aims to explore the potential of intra-anal curcumin as an alternative treatment for aHSIL in people with HIV. The study will involve enrolling participants with aHSIL and administering increasing doses of curcumin intra-anally for 14 days, following the 3 + 3 dose escalation model. The trial will continue until the dose-limiting toxicity (DLT) level is reached, and participants report symptoms necessitating a dose reduction. To enhance future studies, the researchers will also evaluate patient and male partner acceptability through questionnaires. The insights gained from this trial will guide the design of subsequent efficacy and safety studies for individuals with AIN 2 and 3 neoplasia.
Interventions
DRUGCurcuminoid Capsules
500 mg curcuminoids from C3 Complex capsule. Curcuma longa (Turmeric), a constituent of the spice turmeric, is considered a low-toxicity, dietary-derived agent with chemopreventive and therapeutic benefits Study participants will be instructed to insert the curcumin capsules gelatin intra-anally every day for a 14-day treatment period. Escalating doses
Sponsors
Lisa Flowers
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Major Inclusion Criteria: * 30 and older * Have biopsy-proven anal intraepithelial neoplasia (AIN) 2, AIN 3 without previous treatment * Or cytology results for ASC-H or HSIL * Able and willing to complete Study Diary * Other inclusion criteria apply
Exclusion criteria
* Have a clinically significant chronic medical condition that is considered progressive, such as but not limited to coronary disease, congestive heart failure, chronic obstructive lung disease, and diabetes mellitus. Chronic nonprogressive or intermittent syndromes are not excluded, including migraine headaches, mild reactive airway disease, controlled hypertension, stable pain syndromes, or benign gastric reflux. * Have any history of anal cancer malignancy. * Pregnant or planning to become pregnant in the next three months. * Have a history of sensitivity or allergy to any compound used in this study. * Have Grade 2 or higher renal or hematology abnormality, * Are currently using, or in the last year have used intravenous drugs (except for therapeutic use), recreational drugs, or alcohol abuse. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum curcumin tolerated dose | Up to 22 days after treatment | To determine the maximum tolerated dose (MTD) of curcumin, toxicities will be tabulated and reported per dose level according to grade and type of toxicity experienced. The dose level at which no more than 33% of study participants have a DLT will be considered the maximum tolerated dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity related to treatment | Up to 22 days after treatment | Toxicities will be tabulated and reported per dose level according to grade and type of toxicity experienced (tolerability of curcumin). Participants will be monitored during the trial for adverse events, tolerability, and compliance using the Common Terminology Criteria for Adverse Events (CTCAE). Side effects will be recorded in a study diary maintained by the participant. |
| Anoscopy changes | 22 days after treatment | Participants will receive an anoscopy to examine the anus and perineum for any findings outlined in the anoscopic findings chart (Safety of curcumin intra-anal powder) |
Countries
United States
Contacts
CONTACTLisa Flowers, MD, MPH
PRINCIPAL_INVESTIGATORLisa Flowers, MD, MPH
Emory University
Outcome results
None listed