Treatment of Anal High-grade Squamous Intraepithelial Lesions (HSIL) Through Use of a Chinese Herbal Topical Cream

Study Overview
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Brief Summary
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The purpose of this study is to find out if a Chinese herbal cream is effective in treating HSIL (high-grade squamous intraepithelial lesions, also known as HGAIN, or high-grade anal intraepithelial neoplasia).

Detailed Description
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The purpose of this study is to test a new noninvasive topical cream, AIJP (Arnebia Indigo Jade Pearl), for treatment of precancerous anal lesions in order to prevent their progression to anal cancer. AIJP is a topical Chinese herbal cream that has been specifically designed to treat people with the cancer precursor lesions caused by human papillomavirus (HPV). In general, HPV infection is a key factor in development of cervical, anal and vulvar cancers. People with HIV are especially vulnerable to develop anal cancer associated with HPV. It is known that prior to development of anal cancer a person develops a precancerous condition known as a high-grade squamous intraepithelial lesion (HSIL). Treatment of the HSIL can prevent progression to anal cancer. Current therapies for HSIL and anal cancer are highly invasive. A new effective noninvasive topical therapy for precancerous HSIL could have a high impact on prevention of anal cancer.

Official Title
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Phase II Study for Treatment of Anal HSIL Through Use of a Chinese Herbal Topical Cream

Conditions
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Anus Neoplasms

Intervention / Treatment
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* Drug: AIJP (Arnebia Indigo Jade Pearl)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Anal HSIL confirmed by biopsy no more than 30 days prior to entry Anal HSIL deemed not amenable to therapy or participant declines routine ablative therapy HIV positive Stable HIV treatment regimen for at least 8 weeks prior to entry At least 18 years of age Women of childbearing potential must use contraception Platelet count above 70,000/mm3 within 30 days prior to entry ANC greater or equal to 1000/mm3 within 30 days prior to entry Creatinine less then or equal to 1.5 times ULN within 30 days prior to entry AST and ALT less than or equal to 3 times ULN within 30 days prior to entry Exclusion Criteria: Prior history of invasive anal, cervical, vaginal, or vulvar cancer Pregnancy or lactation and breast-feeding Must not participate in a conception process including sperm donation Medical or psychiatric illness that precludes ability to give informed consent or is likely to interfere with ability to comply with protocol Known allergy to any topical cream components Patients with lesions clinically suspicious per HRA examiner for early progression (less than one year) to anal cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: AIJP (Arnebia Indigo Jade Pearl)<br>* Participants will administer their own treatment using 1/4 teaspoon of the cream twice daily for 48 weeks.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo twice daily for 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | Response assessed 12 weeks after treatment. Late Clinical Response (LCR): HSIL present at week 48 but none at week 60, with two independent reviews in agreement that HSIL absent at week 60. Complete response (CR): No HSIL on histology or cytology at weeks 48 or 60 (caveat: if HSIL at week 60, blinded chart notes and photographs were reviewed by two clinicians, and decision was reached by agreement or consensus whether HSIL had been missed at week 48. Cases that reviewers independently agreed had not been missed at week 48 were considered true recurrences) Partial Clinical Response (PCR): HSIL on cytology with no HSIL histology, or improvement >50% in the number of lesions with HSIL, or an improvement >50% in lesion size, area, or clinical characteristics (e.g. acetowhite staining, Lugol's staining, or vascular changes were improved) No Response (NR): HSIL present at weeks 48 & 60 on histology, or improvement ≤ 50% in number, size, area or characteristics. | Baseline, Week 48, and Week 60; up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Adherence | Percent of recommended applications of cream reported in participant diary. >75% = Excellent >50%-75% = Good >25%-50% = Poor <25% = Non-adherent | Up to 48 weeks | 
| Response With >50% Adherence | Response assessed 12 weeks after treatment (week 60), by treatment adherence assessed at 48 weeks. Late Clinical Response (LCR): HSIL present at week 48 but none at week 60; two independent reviews agree HSIL absent at week 60. Complete response (CR): No HSIL on histology or cytology at weeks 48 or 60 (caveat: if HSIL at week 60, blinded chart notes and photographs reviewed by two clinicians, with decision by agreement or consensus whether HSIL had been missed at week 48. Cases that reviewers independently agreed had not been missed at week 48 were considered true recurrences) Partial Clinical Response (PCR): HSIL on cytology with no HSIL histology, or improvement >50% in number of lesions with HSIL, or improvement >50% in lesion size, area, or clinical characteristics (e.g. acetowhite staining, Lugol's staining, or vascular changes improved) No Response (NR): HSIL present on histology, or improvement ≤ 50% in number, size, area or characteristics. | Baseline, Week 48, and Week 60; up to 60 weeks | 
| Response With >75% Adherence | Response assessed 12 weeks after treatment (week 60), by treatment adherence assessed at 48 weeks. Late Clinical Response (LCR): HSIL present at week 48 but none at week 60; two independent reviews agree that HSIL absent at week 60. Complete response (CR): No HSIL on histology or cytology (caveat: if HSIL at week 60, blinded chart notes and photographs were reviewed by two clinicians, and decision was reached by agreement or consensus whether HSIL had been missed at week 48. Cases that reviewers independently agreed had not been missed at week 48 were considered true recurrences) Partial Clinical Response (PCR): HSIL on cytology with no HSIL histology, or improvement >50% in the number of lesions with HSIL, or an improvement >50% in lesion size, area, or clinical characteristics (e.g. acetowhite staining, Lugol's staining, or vascular changes were improved) No Response (NR): HSIL present on histology, or improvement ≤ 50% in number, size, area or characteristics. | Baseline, Week 48, and Week 60; up to 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSIL, HGAIN, AIN, neoplasia, dysplasia, TCM, Traditional Chinese Medicine