Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000154505
Ethics application status
Approved
Date submitted
8/01/2024
Date registered
16/02/2024
Date last updated
4/08/2024
Date data sharing statement initially provided
16/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study of Anal Neoplasia Treatment in people with HIV Evaluation and monitoring (short title: PANTHER)
Scientific title
Pilot study of Anal Neoplasia Treatment in people with HIV Evaluation and monitoring (short title: PANTHER)
Secondary ID [1] 310667 0
HEPP 202301 (study protocol number)
Universal Trial Number (UTN)
Trial acronym
PANTHER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anal High Grade Squamous Intraepithelial Lesions (HSIL) 331570 0
People living with HIV 332687 0
Human Papillomavirus 332688 0
Condition category
Condition code
Surgery 328306 328306 0 0
Surgical techniques
Public Health 329400 329400 0 0
Other public health
Infection 329618 329618 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Anal high grade squamous intraepithelial lesions (HSIL) are caused by high-risk human papillomavirus (HRHPV) and may develop into anal cancer. Anal cancer is rare in the general community, however people who live with HIV (PLHIV) are at higher risk. Anal HSIL is detected by high resolution anoscopy (HRA).

Electrocautery, also known as thermal cautery, refers to a process in which a current is passed through a metal tip/electrode. The heated tip is then applied to the anal HSIL to ablate the tissue and has the advantage of not impacting surrounding normal tissues. During electrocautery, the current only flows through the tip, which burns the tissue by direct transfer of heat. With adequate anaesthesia, the discomfort caused by the treatment will be minimised. The electrocautery procedure takes around 10-20 minutes to perform.

Electrocautery is commonly used in treating skin, eye conditions and other minor surgery. It is currently used in other countries to treat anal HSIL. Until 2023, there was a lack of evidence that treating anal HSIL reduces the risk of anal cancer and most anal HSIL in Australia is closely monitored and not treated.

In this study, study participants will receive up to five electrocautery treatments during a six-month treatment period. There will be one follow-up visit with HRA and biopsy twelve months after the last treatment visit/the last clearance.

Electrocautery treatment will be conducted by sexual health physicians and colorectal surgeons who are trained High Resolution Anoscopists at St Vincent's Hospital Sydney.

Up to five electrocautery treatments will be conducted. There will be a gap of four to six weeks between treatments.

Treatment assessments and electrocautery treatments will be repeated four to six weekly until HSILs have completely cleared at two consecutive assessment visits or participants have received a maximum of five treatments but HSILs have not completely cleared or have not cleared at all.

For example, if a participant has received electrocautery treatment at the Baseline visit (first treatment visit) and their HSILs have completed cleared in two consecutive assessment visits (4–6 weeks apart), they will not require to receive any more treatment. Their next visit will be the follow-up visit.

If their HSILs have partially cleared or not cleared at all after five treatments, they will not receive any more treatments and their next visit will be the follow-up visit.

Adherence to the intervention and post-treatment care is important to the safety and comfort of the participants, and the outcome of the intervention.

Study clinicians will ensure participants understand the research nature of the study, the risks and potential benefits, the implications of their participation, and the importance of adhering to the intervention during the informed consent process. Participants will be provided with written and verbal information of how to prepare for the electrocautery treatment and the after care to reduce discomfort or the likelihood of adverse events. Discomfort during treatment will be minimised by numbing agents in the form of cream and injections and study clinicians will ensure the participants have adequate pain cover.

Participants will be completing a symptom diary after each treatment and their symptoms/adverse events will be closely monitored and addressed by their study clinicians to help adherence.

The study research assistant at St Vincent’s Hospital will follow-up with participants if they miss any scheduled appointments and refer them to the study clinicians if participants have any concern of returning to the clinic for subsequent visits.

However, study clinicians will make it very clear to the participants that they can withdraw at any time during the study if they changed their mind or if their situation changed and they no longer wanted to receive the study treatment or attend any study visits. They will be assured that withdrawal from participation will not affect their ongoing care at the clinic.


Intervention code [1] 327073 0
Treatment: Surgery
Intervention code [2] 327898 0
Prevention
Comparator / control treatment
There is no control group in this study. All study participants will receive up to five electrocautery treatments during the study in a six-month period.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336176 0
Participation rate of eligible patients in the study.
Timepoint [1] 336176 0
At the end of recruitment.
Primary outcome [2] 336177 0
Complete clearance of intra-anal HSIL after treatment.
Timepoint [2] 336177 0
These endpoints will be measured 12 months after HSIL clearance in people who clear HSIL in the first 6 months.
Primary outcome [3] 337258 0
Partial intra-anal HSIL clearance after treatment.
Timepoint [3] 337258 0
The endpoint will be measured 12 months after the last treatment in people who do not completely clear HSIL during the first 6 months.
Secondary outcome [1] 427213 0
Type-specific HRHPV clearance will be assessed in participants who have at least one type of HRHPV detected at study baseline, after treatment. For each HRHPV type, the study will calculate the proportion of participants who cleared that specific HRHPV type at their last study visit among those who have this HRHPV type detected at baseline.
Timepoint [1] 427213 0
The endpoint will be measured 12 months after HSIL clearance (in people who clear HSIL in the first 6 months) or 12 months after the last treatment (in people who do not clear HSIL during the first 6 months).
Secondary outcome [2] 427214 0
Frequency and severity of adverse events.
Timepoint [2] 427214 0
Adverse events data will be collected at the Baseline visit (first treatment visit) and at all treatment and assessment visits (four to six weeks apart), and at the follow-up visit, which is 12 months after HSIL clearance (in people who clear HSIL in the first 6 months) or 12 months after the last treatment (in people who do not clear HSIL during the first 6 months).
Secondary outcome [3] 427215 0
Participant experience of electrocautery as an anal HSIL treatment by conducting post-treatment questionnaire and a final study questionnaire.
Timepoint [3] 427215 0
Post-treatment questionnaire will be completed by all participants 2 weeks after each treatment. Final study questionnaire will be completed by all participants at the follow-up visit, which is 12 months after HSIL clearance (in people who clear HSIL in the first 6 months) or 12 months after the last treatment (in people who do not clear HSIL during the first 6 months).
Secondary outcome [4] 431236 0
In-depth participant experience of electrocautery as an anal HSIL treatment by conducting an optional qualitative interview in a subgroup of participants.
Timepoint [4] 431236 0
The Baseline visit is the first treatment visit, end of treatment visit is the last treatment visit, and the follow-up visit is 12 months after HSIL clearance (in people who clear HSIL in the first 6 months) or 12 months after the last treatment (in people who do not clear HSIL during the first 6 months.

Eligibility
Key inclusion criteria
1. Aged 18 years or older
2. Documented HIV positive
3. Current patient of the Dysplasia and Anal Cancer Services (DACS) clinic under active follow-up
4. Histologically established persistent intra-anal HSIL of 4 or fewer octants diagnosed on 2 or more occasions, OR intra-anal HSIL considered by study doctor to be eligible for treatment
5. Willing to not undergo any other anal HSIL therapeutic interventions while taking part in the study. Treatment for anal conditions other than HSIL (such as dermatological abnormalities) may be allowed with the permission of the study doctor.
6. Able to provide written informed consent
7. No planned absences during the first 6 months of follow-up.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of any other HSIL treatment within 3 months prior to the Baseline visit
2. Any perianal HSIL diagnosed, alone or in conjunction with intra-anal HSIL
3. Substantial quantity of anal verge HSIL subject to clinicians’ discretion
4. Intra-anal exophytic low-grade lesions, the extent of which compromises the ability to deliver effective electrocautery
5. Any anal or rectal pathology such as ulcer, fistula, stricture, or stenosis that, in the clinician’s assessment, is likely to adversely affect the efficacy of treatment
6. Concurrent malignancy requiring systemic therapy
7. At the clinician’s discretion, whether the participant is on a platelet inhibiting agent (e.g., Clopidogrel) and/or anti-thrombotic agent (e.g., Heparin or Rivaroxaban) and unable to discontinue 7 days before and after treatment for 14 days total.
o Exception: Aspirin 100 mg PO daily does not need to be discontinued
8. Undergoing Warfarin therapy
9. Pregnant or planning to become pregnant during the treatment period
10. Unwilling to comply with study-related procedures
11. Unable to undergo or tolerate the HRA procedure.
12. Has a pacemaker.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive analyses will be used to determine willingness to undergo HSIL treatment, HSIL clearance, and HRHPV clearance.

To account for potential mucosal shifts in between HRA procedures, a lesion in the same octant, or in either of the two octants on each side of the index location will be considered the same location for the purpose of statistical analyses.

Sample size: at least 112 eligible potential participants will be approached, based on the assumption that the participation rate will be approximately 80%. If necessary, more participants will be approached to achieve a treated cohort of 100.

The rates of complete and partial clearance will be calculated at the last final study visit as assessed by the presence of HSIL in the anal canal.

Complete clearance will be assessed as the proportion of participants who have no HSIL detected in the anal canal at their last final study visit.

Partial HSIL clearance will be assessed as the proportion of participants who achieve the clearance of at least one index anal HSIL or in participants who have cleared all treated HSIL but have HSIL detected in other distinctive areas of the anal canal.

Type-specific HRHPV clearance will be determined in participants who have at least one type of HRHPV detected at study baseline.

In addition, the mean number of octants affected by HSIL, and the total surface affected will be compared between study baseline and at the final study visit using a t-test; p values will be presented.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/04/2024
Actual
28/05/2024
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
31/08/2026
Actual
Sample size
Target
100
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25588 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 41411 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 314887 0
Charities/Societies/Foundations
Name [1] 314887 0
Glendonbrook Foundation
Country [1] 314887 0
Australia
Primary sponsor type
University
Name
University of New South Wales Sydney, NSW, Australia
Address
The Kirby Institute, University of New South Wales, Sydney, Wallace Wurth Building, NSW 2052
Country
Australia
Secondary sponsor category [1] 316905 0
None
Name [1] 316905 0
Address [1] 316905 0
Country [1] 316905 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313883 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 313883 0
Ethics committee country [1] 313883 0
Australia
Date submitted for ethics approval [1] 313883 0
22/09/2023
Approval date [1] 313883 0
21/12/2023
Ethics approval number [1] 313883 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129662 0
Dr Mary Poynten
Address 129662 0
The Kirby Institute, University of New South Wales Sydney, Wallace Wurth Building, Sydney, NSW 2052
Country 129662 0
Australia
Phone 129662 0
+61 2 9385 0900
Fax 129662 0
+61 2 9385 0920
Email 129662 0
[email protected]
Contact person for public queries
Name 129663 0
Mary Poynten
Address 129663 0
The Kirby Institute, University of New South Wales Sydney, Wallace Wurth Building, Sydney, NSW 2052
Country 129663 0
Australia
Phone 129663 0
+61 2 9385 0900
Fax 129663 0
+61 2 9385 0920
Email 129663 0
[email protected]
Contact person for scientific queries
Name 129664 0
Mary Poynten
Address 129664 0
The Kirby Institute, University of New South Wales Sydney, Wallace Wurth Building, Sydney, NSW 2052
Country 129664 0
Australia
Phone 129664 0
+61 2 9385 0900
Fax 129664 0
+61 2 9385 0920
Email 129664 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No IPD will be shared. Study results will be published in peer-reviewed medical and scientific journals, presentations at conferences or other professional forums.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.