Anus Neoplasms
Conditions
Keywords
HSIL, HGAIN, AIN, neoplasia, dysplasia, TCM, Traditional Chinese Medicine
Brief summary
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
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.
Interventions
DRUGAIJP (Arnebia Indigo Jade Pearl)
Participants will administer their own treatment using 1/4 teaspoon of the cream twice daily for 48 weeks.
DRUGPlacebo
Placebo twice daily for 48 weeks.
Sponsors
Spring Wind Herbs
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | Baseline, Week 48, and Week 60; up to 60 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Adherence | Up to 48 weeks | Percent of recommended applications of cream reported in participant diary. \>75% = Excellent \>50%-75% = Good \>25%-50% = Poor \<25% = Non-adherent |
| Response With >50% Adherence | Baseline, Week 48, and Week 60; up to 60 weeks | 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. |
| Response With >75% Adherence | Baseline, Week 48, and Week 60; up to 60 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AIJP AIJP (Arnebia Indigo Jade Pearl): Participants administer 1/4 teaspoon of AIJP cream twice daily for 48 weeks. | 35 |
| Placebo Placebo: Participants administer 1/4 teaspoon of placebo cream twice daily for 48 weeks. | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline - Week 12 (Treatment) | Received cream but did not return | 4 | 1 |
| Week 12 - Week 48 (Treatment) | Lost to Follow-up | 3 | 5 |
| Week 12 - Week 48 (Treatment) | Not evaluable - censored from dataset | 0 | 1 |
| Week 60 (Post-treatment Follow-up Visit) | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | AIJP | Placebo | Total |
|---|---|---|---|
| Age, Customized 24-39 years | 5 participants | 10 participants | 15 participants |
| Age, Customized 40-59 years | 25 participants | 22 participants | 47 participants |
| Age, Customized 60-74 years | 5 participants | 3 participants | 8 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 32 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 24 Participants | 56 Participants |
| Region of Enrollment United States | 35 participants | 35 participants | 70 participants |
| Sex/Gender, Customized Men | 34 participants | 33 participants | 67 participants |
| Sex/Gender, Customized MTF (transgender) | 0 participants | 1 participants | 1 participants |
| Sex/Gender, Customized Women | 1 participants | 1 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 1 / 35 |
Outcome results
Primary
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.
Time frame: Baseline, Week 48, and Week 60; up to 60 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIJP | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | LCR | 3 participants |
| AIJP | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | CR | 7 participants |
| AIJP | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | PCR | 5 participants |
| AIJP | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | NR | 13 participants |
| Placebo | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | NR | 19 participants |
| Placebo | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | LCR | 0 participants |
| Placebo | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | PCR | 6 participants |
| Placebo | Final Response of Anal High-grade Squamous Intraepithelial Lesions (HSIL) | CR | 3 participants |
Comparison: Estimated Effect Size for Phase 3 Trialp-value: 0.042Wilcoxon rank sum
Secondary
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.
Time frame: Baseline, Week 48, and Week 60; up to 60 weeks
Population: Evaluable participants who finished 48 weeks of treatment and reported \>50% adherence to treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIJP | Response With >50% Adherence | PCR | 4 participants |
| AIJP | Response With >50% Adherence | NR | 12 participants |
| AIJP | Response With >50% Adherence | LCR | 3 participants |
| AIJP | Response With >50% Adherence | CR | 7 participants |
| Placebo | Response With >50% Adherence | CR | 3 participants |
| Placebo | Response With >50% Adherence | PCR | 5 participants |
| Placebo | Response With >50% Adherence | LCR | 0 participants |
| Placebo | Response With >50% Adherence | NR | 13 participants |
Secondary
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.
Time frame: Baseline, Week 48, and Week 60; up to 60 weeks
Population: Evaluable participants who finished 48 weeks of treatement and reported \>75% adherence to treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIJP | Response With >75% Adherence | LCR | 3 participants |
| AIJP | Response With >75% Adherence | PCR | 2 participants |
| AIJP | Response With >75% Adherence | NR | 7 participants |
| AIJP | Response With >75% Adherence | CR | 5 participants |
| Placebo | Response With >75% Adherence | NR | 9 participants |
| Placebo | Response With >75% Adherence | LCR | 0 participants |
| Placebo | Response With >75% Adherence | CR | 1 participants |
| Placebo | Response With >75% Adherence | PCR | 5 participants |
Secondary
Treatment Adherence
Percent of recommended applications of cream reported in participant diary. \>75% = Excellent \>50%-75% = Good \>25%-50% = Poor \<25% = Non-adherent
Time frame: Up to 48 weeks
Population: Excludes 7 AIJP participants and 6 Placebo participants who dropped out before week 48. Excludes 1 Placebo participant deemed non-evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIJP | Treatment Adherence | Good | 9 participants |
| AIJP | Treatment Adherence | Excellent | 17 participants |
| AIJP | Treatment Adherence | Poor | 1 participants |
| AIJP | Treatment Adherence | Non-adherent | 1 participants |
| Placebo | Treatment Adherence | Non-adherent | 3 participants |
| Placebo | Treatment Adherence | Excellent | 15 participants |
| Placebo | Treatment Adherence | Good | 6 participants |
| Placebo | Treatment Adherence | Poor | 4 participants |