A trial looking at higher doses of chemoradiotherapy for people with locally advanced anal cancer (PLATO ACT5)

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Cancer type:

Anal cancer

Status:

Open

Phase:

Phase 3

This trial is for people whose anal cancer is bigger than 4 cm or has spread to the lymph nodes (locally advanced). It is comparing standard with higher doses of chemoradiotherapy.

Cancer Research UK supports this trial. 

More about this trial

People with locally advanced anal cancer often have treatment with a combination of chemotherapy and radiotherapy (chemoradiotherapy).

Radiotherapy uses high energy x-rays to kill anal cancer cells. You also have chemotherapy at the same time. There are different drugs you can have such as:

This is the standard treatment Open a glossary item.

We know from previous research that people with locally advanced anal cancer have a higher risk of the cancer coming back. So doctors want to find out if having a higher dose of chemoradiotherapy is better than the standard dose at curing anal cancer and stopping it from coming back.

This trial is in 3 parts. In part 1 the researchers are looking at the side effects of the higher dose of chemoradiotherapy. Then they will look for the best higher dose of chemoradiotherapy (part 2). Doctors will decide the best higher dose by looking at the side effects and at how the treatment works. In part 3 researchers are comparing the best higher dose found with the standard treatment.

People in part 1 and 2 have one of the following:

  • standard dose of chemoradiotherapy
  • higher dose of chemoradiotherapy
  • slightly higher dose of chemoradiotherapy

People in part 3 have one of the following:

  • standard dose of chemoradiotherapy
  • best higher dose of chemoradiotherapy

The main aims of this trial are to:

  • learn about the side effects of the higher dose of chemoradiotherapy
  • find out the best higher dose of chemoradiotherapy
  • find out if a higher dose of chemoradiotherapy is better than the standard dose 

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

You may be able to join this trial if all of the following apply.

  • You have squamous cell cancer of the anus that is bigger than 2 cm (T2 or T3) or has spread to the lymph nodes Open a glossary item 
  • You have satisfactory blood tests results
  • Your doctor thinks you are well enough to have chemoradiotherapy
  • You are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)   
  • You are at least 16 years old
  • You are willing to use reliable contraception during treatment and for 6 months afterwards if there is any possibility you or your partner could become pregnant

You cannot join this trial if any of these apply.

Cancer related

  • Your cancer has spread to other parts of the body (apart from the lymph nodes)
  • You have had chemotherapy that reached your whole body (systemic) as a treatment for anal cancer
  • You have had radiotherapy to the area between your hip bones (pelvis)
  • You have had treatment for another cancer in the last 2 years (your doctor can tell you more about this)

Medical conditions

  • You have heart problems such as angina that isn’t controlled or you have had a heart attack in the past 6 months
  • You have had an organ transplant Open a glossary item

Other

  • You are not able to have an MRI scan for any reason, for example you have metal implants such as a pacemaker, surgical clips, implants, pins, plates, you have a fear of being in closed spaces (claustrophobia) or you are allergic to the dye (contrast medium Open a glossary item) given during the scan
  • You are pregnant or breastfeeding

Trial design

Part 1 of this trial is a pilot study. Researchers hope that about 60 people will join the pilot study. Part 2 is a phase 2 trial. The research team need more 80 people for this part.

Both parts are randomised. Everyone is put into 1 of the following treatment groups by computer:

  • standard dose of chemoradiotherapy  
  • higher dose of chemoradiotherapy
  • slightly higher dose of chemoradiotherapy

Neither you nor your doctor will be able to decide which group you are. 

PLATO ACT5 Diagram

Part 3 is a phase 3 trial. Researchers need 500 people for phase 3. This part is also randomised. Everyone is put into 1 of the following treatment groups by computer:

  • standard dose of chemoradiotherapy
  • best higher dose of chemoradiotherapy

Neither you nor your doctor will be able to decide which group you are. 

PLATO ACT5 Diagram 2

Radiotherapy
You have a CT scan. This is a radiotherapy planning scan. The scan helps the doctors know how much radiation you need and exactly where you need it. The amount of radiotherapy you have (the dose) depends on the group you join.

After about 2 weeks you start the radiotherapy. You have it every day, Monday to Friday, with a break at weekends. Each treatment takes about 10 to 20 minutes. You have 28 treatments (around 5 ½ weeks). 

Chemotherapy
You have chemotherapy at the same time you have radiotherapy. You have a combination of 2 drugs:

  • mitomycin C
  • capecitabine or fluorouracil

Mitomycin C is an injection you have into your vein. You have it on the 1st day of radiotherapy.

Capecitabine comes as tablets that you take twice a day, morning and evening. You take them each day you have radiotherapy.

Fluorouracil is a continuous infusion. You have it via a pump over 4 days, during week 1 and week 5 of radiotherapy.

Your doctor can tell you if you will have capecitabine or fluorouracil. It depends on what your hospital use.

Stoma
You might need a surgery to form an opening from the bowel onto the surface of your tummy (a colostomy or ileostomy) before the start of treatment. This is because your doctor thinks that you might have problems with your bowels during treatment.

This is routine (standard) care. Your doctor can tell you if you need this.

Quality of life
You complete quality of life questionnaires:

  • at the time you join the trial
  • at the end of treatment
  • 6 weeks after the end of treatment
  • then after 6 months, 1, 2 and 3 years

The questionnaires ask about how you have been feeling and what side effects you have had. They take about 15 minutes to complete each time. You can complete the questionnaires online or on paper.

Tissues samples, blood samples and scans
The trial team might ask:

  • to use a tissue sample of your cancer taken when you were diagnosed (stored biopsies)
  • to use a tissue sample of your cancer taken when you join this trial and if your cancer gets worse (if you have samples of tissue taken as part of your routine care) 
  • to have up to 6 extra blood tests at set times during this trial 
  • for your permission to look at the scans taken as part of this trial

They want to study more about anal cancer, find out who is at risk of it and who is most likely to have side effects from treatment.

You don’t have to agree to this if you don’t want to. You can still take part in this trial.

Your name and address will be removed from the scans and the tissue sample. So no one will be able to identify you. 

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

  • a physical examination
  • blood tests
  • a heart trace (ECG Open a glossary item)
  • a CT scan
  • an MRI scan
  • a PET scan Open a glossary item

You see the trial doctor for blood tests and a physical examination every week during treatment.

When you finish treatment, you see the trial doctor after 6 weeks. Then:

  • every 3 months for the first 2 years
  • every 6 months for 1 year
  • once a year (your doctor can tell you for how long)

You have an MRI scan after 3 and 6 months of the end of treatment. And a CT scan every year, for 3 years. 

Side effects

The trial team monitor you during the time you have treatment and you have a phone number to call them if you are worried about anything.  The team will tell you about all the possible side effects before you start the trial.

Radiotherapy to the anus has short term (or acute) side effects that usually start a few days after the radiotherapy begins. And side effects that can start some months or years later (long term or late side effects). 

The most common short term side effects of radiotherapy include:

  • sore skin
  • diarrhoea
  • problems passing urine- it might be difficult or painful to pass urine or you might have some incontinence Open a glossary item
  • loss of pubic hair
  • tiredness (fatigue)
  • vaginal irritation

We have more information about short term radiotherapy side effects.

And information about long term radiotherapy side effects.

The most common side effects of chemotherapy include:

  • drop in blood cells causing an increased risk of infection, bruising or bleeding 
  • feeling orfeeling or being sick
  • sore mouth

We have more information about the side effects of:

Location

Aberdeen
Birmingham
Brighton
Bristol
Cambridge
Cardiff
Cheltenham
Coventry
Edinburgh
Exeter
Glasgow
Guildford
Hull
Leeds
London
Manchester
Newcastle upon Tyne
Northwood
Nottingham
Oxford
Preston
Rhyl
Sheffield
Southampton
Sutton
Swansea
Wirral

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor David Sebag-Montefiore 

Supported by

Cancer Research UK
University of Leeds 

Other information

This is Cancer Research UK trial number CRUK/15/007.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14592

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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