A trial to establish whether laser treatment of anal precancer prevents development of anal cancer in HIV-positive men who have sex with men
| ISRCTN | ISRCTN14067023 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14067023 |
| EudraCT/CTIS number | 2015-002806-36 |
| Secondary identifying numbers | 19230 |
- Submission date
- 15/07/2015
- Registration date
- 15/07/2015
- Last edited
- 24/05/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Background and study aims
Anal cancer is a growing problem in the UK. Almost 90% of these cancers are caused by the human papillomavirus (HPV). HPV infection in a weakened immune system can lead to abnormal cell changes which are graded as anal intraepithelial neoplasia (AIN) 1-3, with AIN 2 and AIN 3 considered to be high-grade neoplasia (AIN 2/3). These changes are called precancers, but it is not known how many, over what time period will turn to cancer. Although many doctors and scientists think we need to treat AIN 2/3 (precancer), as is done in women for cervical precancer to prevent cancer, there is no proven treatment for anal precancer (AIN 2/3) that will prevent anal cancer. Laser treatment may be an effective strategy to prevent anal cancer. The main aim of the study is to assess the long-term effect (up to 5 years) of laser treatment in preventing anal cancer in HIV-positive men who have sex with men with anal precancer.
Who can participate?
HIV-positive men who have sex with men, who have anal precancer
What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the treatment group undergo laser ablation of their perianal (external) or anal canal (internal) disease under local anaesthetic injections. If the disease volume (extent) is large the ablation may be done under general anaesthetic as a day case. Rarely, it may be necessary to treat extensive disease as a staged procedure over more than one treatment visit. Participants in the active surveillance group receive no treatment. All participants are followed up every 6 months with standard examinations. The number of cancers, the effect of treatment on preventing new precancer, quality of life, and the costs of treatment are compared between the groups.
What are the possible benefits and risks of participating?
The main ethical issue is that participants in the surveillance group are not treated, but this is justified for two reasons. First, there is no proven treatment and standard care at present is a 'watch and wait approach' (observation). Second, patients in the surveillance group have the benefit of regular examination, which is not routinely available in the UK. With regular examination every 6 months, anal cancer can be diagnosed at a very early stage, when treatment is less radical and clinical outcomes are excellent (85-90% survival at 5 years). If anal canal lumps are identified at any study visit or through patient self-examination in between visits, the participants are seen at short notice to exclude cancer and referred on to treatment if cancer is found.
Where is the study run from?
1. Homerton Hospital Anal Neoplasia Service (HANS) (UK)
2. Bloomsbury Clinic, Mortimer Market Centre (UK)
When is the study starting and how long is it expected to run for?
October 2014 to September 2021
Who is funding the study?
National Institute of Health Research (NIHR) (UK)
Who is the main contact?
Jennifer Child
Contact information
Public
Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom
 ORCID ID |
0000-0001-5115-8164 |
|---|
Study information
| Study design | Randomised; Interventional and Observational; Design type: Diagnosis, Prevention, Screening, Treatment, Cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomised controlled trial to study the effectiveness of Laser ablation versus Observation to Prevent Anal Cancer in men who have sex with men with human immunodeficiency virus infection who have high-grade anal intraepithelial neoplasia (AIN 2 and/or AIN 3) disease |
| Study acronym | LOPAC |
| Study hypothesis | The LOPAC study will endeavor to answer the question if active treatment of high-grade AIN disease may prevent progression to anal cancer. |
| Ethics approval(s) | NRES Committee London – London Bridge, 02/07/2015, ref: 15/LO/0942 |
| Condition | Topic: Cancer; Subtopic: Colorectal Cancer; Disease: Anus |
| Intervention | The treatment being tested is laser ablation. This involves burning the skin/other similar lining using laser where anal precancer was identified and involves a local burn. Patients in the treatment arm will receive up to four courses of laser treatment during the trial period, performed by one of the clinicians at Homerton University Hospital NHS Foundation Trust. Follow Up Length: 72 month(s); Study Entry : Single Randomisation only |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Incidence of anal cancer in treatment arm compared to observation arm through the trial period; Timepoint(s): Over course of trial = 72 months |
| Secondary outcome measures | For all enrolled participants: 1. The rates of AIN 2 and/or AIN 3 detected in the population enrolled into the study.; Timepoint(s): Over the course of trial = 72 months 2. Risk factors for AIN 2 and/or AIN 3 and knowledge about HPV and anal cancer in participants with AIN2 and/or AIN3, compared to those who screened negative for AIN2 and/or AIN3 disease.; Timepoint(s): Over the course of the trial = 72 months For all randomised participants: 3. Proportion of clearance/regression/progression of high-grade AIN lesions in the treatment arm, compared to the observation arm.; Timepoint(s): Over the course of the trial = 72 months 4. Incidence of metachronous (new) lesions and the rate of recurrence of high-grade AIN disease after clearance in the treatment arm, compared to the observation arm.; Timepoint(s): Over the course of the trial = 72 months 5. Difference, if any, by quadrants of high-grade AIN disease in the treatment arm, compared to the observation arm as measured by the proportion of disease clearance/regression/progression.; Timepoint(s): Over the course of the trial = 72 months 6. Number of treatment episodes/treatment duration needed to clear high-grade AIN lesions, by quadrants of disease in the treatment arm. ; Timepoint(s): Over the course of the trial = 72 months 7. Proportion free of high-risk HPV types in the treatment arm, compared to the observation arm, at the end of the study. ; Timepoint(s): At end of trial = at 72 months 8. Incidence of anal cancer in the treatment arm compared to the observation arm stratified by HPV 16 detection. ; Timepoint(s): Over the course of the trial = 72 months 9. Health-related quality of life, as measured by Area Under the Curve for EQ-5D, in the treatment c compared to the observation arm at each visit post-randomisation. ; Timepoint(s): Over the course of the trial = 72 months 10. Health-related quality of life, as measured by Area Under the Curve for EQ-5D, in the treatment arm only, 1 month post-laser ablation; Timepoint(s): Over the course of the trial = 72 months 11. Total cost of each anal cancer case prevented (including equipment costs and clinic visits). ; Timepoint(s): Over the course of the trial = 72 months 12. A model of AIN grading, progression, regression and clearance as a result of laser ablative treatment. ; Timepoint(s): Over the course of the trial = 72 months For all trial participants: 13. Anal cancer rates up to 40 years after enrolment in the screened, treated and surveillance patient groups (through a future ethically approved study). ; Timepoint(s): Up to 40 years after enrolment (as part of a future ethically-approved study) |
| Overall study start date | 01/10/2014 |
| Overall study end date | 30/09/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target number of participants | Planned Sample Size: 3500; UK Sample Size: 3500; Description: We are screening about 3,500 participants. Those without high-grade anal precancer disease will not be asked to attend again. All participants found to have histology-proven high-grade precancer will be invited to continue into the second part of the trial. 660 participants with high-grade AIN disease from the 3,500 enrolled patients will be randomised 1:1 into the treatment and observation arms (N= 330 in each arm). |
| Participant inclusion criteria | 1. HIV-positive men who have sex with men (MSM) over 18 years of age (HIV status confirmed by patient’s HIV unit) 2. CD4 cell count of 350cells/µl or greater within twelve months of randomisation; if CD4 count is less than 350cells/µl the patient must be on highly active antiretroviral treatment for at least three months, confirmed by patient’s HIV unit 3. Not currently enrolled in any other intervention study about AIN or anal cancer 4. Willing to attend Homerton University Hospital NHS Foundation Trust for all treatment and follow up appointments if allocated to treatment arm of the study 5. Physical and mental capacity to give informed consent 6. Necessary level of verbal and/or reading comprehension of English to give informed consent Only patients with histologically proven AIN2 and/or AIN 3 disease within the previous four months will be eligible for randomisation for the second part of the trial |
| Participant exclusion criteria | 1. Previous laser or other ablative treatment for AIN/warts in both the anal and perianal regions (cryotherapy if NOT an exclusion critera; if they previously had ablative treatment for external AIN disease/warts and now present with untreated anal canal disease they will be eligible; and similarly, if they had previous anal canal ablative treatment for AIN disease/warts and now present with untreated external disease, they will be eligible to participate in the trial) 2. Any other topical or surgical treatment for AIN 2 and/or AIN 3 or anal/perianal warts in the previous six months 3. Previous or current diagnosis of anal cancer or under investigation for anal cancer 4. Unable or unwilling to attend treatment and followup visits at the Homerton hospital (if randomised to treatment arm) or follow up visits at their recruiting site (if randomised to observation arm) |
| Recruitment start date | 04/12/2015 |
| Recruitment end date | 02/01/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Clifden Centre
Homerton Row
London
E9 6SR
United Kingdom
WC1E 6JB
United Kingdom
Sponsor information
Hospital/treatment centre
Homerton University Hospital NHS Foundation Trust
Clifden Centre
Homerton Row
London
E9 6SR
England
United Kingdom
| christine.inwang@homerton.nhs.uk | |
| Website | http://www.homerton.nhs.uk/ |
"ROR" |
https://ror.org/00x444s43 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
24/05/2019: Internal review.
23/02/2018: Plain English summary added.
28/09/2015: The overall trial end date was changed from 17/12/2021 to 30/09/2021.
