A trial looking at ATRA and chemotherapy for pancreatic cancer

Cancer type:

Pancreatic cancer

Status:

Open

Phase:

Phase 1

This trial is for people with pancreatic cancer that has grown into surrounding tissue (locally advanced), or spread to another part of the body.

More about this trial

Chemotherapy is the usual treatment for pancreatic cancer that has spread. One combination of chemotherapy is gemcitabine and nab-paclitaxel. Nab-paclitaxel is the chemotherapy drug paclitaxel combined with a protein called albumin. It is also called Abraxane.

Chemotherapy may slow the growth of the cancer and stop if from spreading further. But doctors would like to improve on this. If treatment shrinks the cancer enough, some people could have surgery to remove their pancreatic cancer.

Doctors would like to find out if a drug called ATRA improves treatment. ATRA is similar to vitamin A and is already used to treat a type of leukaemia. ATRA is also called tretinoin or Vesinoid.

Pancreatic cancer is surrounded by thick scar tissue called stroma. This can block chemotherapy drugs from reaching the cancer.

Pancreatic stellate cells (PSCs) are part of the stroma. Cancer activates these PSCs, which then help cancer cells to survive and spread. In their normal state, PSCs store vitamin A.  When they become activated by cancer, they lose the vitamin A.

Laboratory research has shown that giving vitamin A can change the PSCs back to normal. This might allow the chemotherapy to get to the cancer cells. This needs to be tested in people with cancer.

The aims of this trial are to:

  • find the best dose of ATRA, gemcitabine and nab-paclitaxel when given together
  • learn more about the side effects

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.

  • A sample (biopsy Open a glossary item) of your cancer has shown that you have ductal adenocarcinoma of the pancreas
  • You must have a sample of your cancer available for the team to use as part of this research. If a sample is not available, you must be willing to have a biopsy
  • You have pancreatic cancer that has grown into surrounding tissue (locally advanced), or spread to another part of your body (metastatic)
  • You have an area of cancer that can be measured
  • You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • You have satisfactory blood test results
  • You are willing to use reliable contraception during treatment in the trial if there is any chance that you or your partner could become pregnant. You should also use reliable contraception for 1 month following treatment if you are female and for 6 months following treatment if you are male
  • You are aged at least 18 years

You cannot join this trial if any of these apply. You

  • Have already had treatment that reaches the whole body (systemic therapy Open a glossary item) for locally advanced or metastatic pancreatic cancer. You may be able to take part if you had chemotherapy after your surgery (adjuvant therapy Open a glossary item) and this was at least 6 months ago
  • Have cancer that has spread to your brain
  • Have problems with numbness and tingling in your hands and feet (peripheral neuropathy Open a glossary item)
  • Have certain heart problems, such as a heart attack in the last year
  • Have certain lung conditions such as interstitial lung disease, sarcoidosis, silicosis, pneumonitis
  • Have  a connective tissue disorder such as lupus or scleroderma disease
  • Have a condition called peripheral artery disease where the arteries narrow, affecting the blood supply to muscles, mainly in the legs
  • Have had any other cancer in the last 5 years, unless it was very early stage and has been successfully treated with surgery or surgery and radiotherapy
  • Have an infection which needs treating
  • Have active hepatitis B or C
  • Have HIV
  • Have food allergies, including soya bean or peanut allergies, or you are allergic to the drugs used in this trial
  • Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
  • Have had treatment as part of a trial in the last 4 weeks
  • Have had a live vaccination in the last 4 weeks
  • Are taking supplements containing vitamin A and you are not willing to stop these
  • Are pregnant or breast feeding

Trial design

This is a phase 1 trial. The researchers need up to 34 people to join. This trial has 2 parts. The first part has now closed to recruitment.and the 2nd part is now recruiting.

Part 1
In part 1, the first few people had a low dose of ATRA, gemcitabine and nab-paclitaxel. If they didn’t have any serious side effects, the next few people had a higher dose. And so on, until the doctors found the best dose. This is called a dose escalation study.

Part 1 looked at:

  • 3 different doses of ATRA
  • 2 different doses of both gemcitabine and nab-paclitaxel

The dose people had of each drug depended on when they joined the trial. 

Part 2
In part 2, everyone has the best dose of each drug found in the first part of the trial.

You have gemcitabine and nab-paclitaxel through a drip into a vein every week for 3 weeks. In the 4th week you have no drugs into your vein. Each 4 week period is called a cycle of treatment.

You have gemcitabine and nab-paclitaxel for as long as it is helping you. And as long as you don’t have any severe side effects.

ATRA comes as a capsule. You take it twice as day (12 hours apart) for the first 15 days of each cycle. Then you have a break for 13 days. You have ATRA for 6 cycles (about 6 months).

As well as routine blood tests, you have a blood test as part of this trial at the end of each cycle. The researchers look for different things, including biomarkers, and to find out the level of vitamin A in your blood. Depending on your result, you may be asked to take a lower or higher dose of ATRA. This is to make sure that you have the correct dose of ATRA.

A new sample of your cancer
Before treatment starts, the researchers ask your permission to look at a sample of your cancer. If you don’t have stored sample available, you would need to have a biopsy taken of your cancer in order to take part in this trial.

The researchers also ask you to have a new biopsy of your cancer:

  • during cycle 3 of treatment
  • if there are signs that your cancer has started to grow

These samples are optional, you don’t have to agree to this part of the trial if you don’t want to. 

All of these cancer samples will be used to look for biomarkers Open a glossary item to find out why treatment might work for some people and not for others.

A swab from your mouth and a sample of your hair
You have a small brush rubbed on the inside of your mouth and some hairs removed from your head or eyebrows. You provide these samples:

  • during cycle 1 of treatment
  • during cycle 3 of treatment
  • if there are signs that your cancer has started to grow

These samples will be used to look at different things including what happens to ATRA, gemcitabine and nab-paclitaxel in your body and to look for biomarkers.

You don’t have to give these extra samples if you don’t want to. You can still take part in the trial.

Diffusion weighted MRI scan
You are asked to have a new type of MRI scan on 3 different occasions. Two of these will be before your treatment and the third during your treatment.

You must agree to have these scans if you are in part 2 of the trial. This is as well as any scans you may need as part of your routine care.

The trial team want to find out how useful the Diffusion Weighted MRI scan (DW-MRI) is. Each scan takes about 30 minutes. Before treatment you have a 30 minute scan followed by a 15 minute scan, with a short coffee break in between.

This new scan may provide information about:

  • how chemotherapy works in combination with ATRA
  • how scar tissue changes
  • how cancer cells die as a result of treatment

You don’t have to have these extra scans if you don’t want to. The results will not be used to make decisions about your treatment. But the information they provide may improve the way doctors can see how well treatment is working in the future. 

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include:

  • physical examination
  • blood tests
  • heart trace (ECG Open a glossary item)
  • CT scan or MRI scan of your cancer

You see a doctor regularly during your treatment. They will examine you and ask if you have any side effects. You have blood tests nearly every week during treatment. You have a scan of your cancer every 2 months.

One month after you finish treatment, you go to hospital for your final appointment as part of this trial. You have blood tests and a further scan.

The trial team will then collect information about you when you have routine clinic appointments every 3 months until you have been on the trial for 1 year. This will include information about your cancer and any side effects you have.

Side effects

The most common side effects of ATRA include:

We have more information about ATRA.

The side effects of gemcitabine and nab-paclitaxel include:

  • a drop in blod cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
  • numbness and tingling in your hands and feet (peripheral neuropathy)
  • hair loss  
  • feeling or being sick 
  • swelling of ankles, fingers or feet – this usually goes away on its own, but tell your doctor or nurse if it is a problem
  • diarrhoea 
  • constipation 
  • skin rash
  • headaches
  • feeling dizzy
  • feeling depressed
  • aching joints and aching muscles
  • taste changes and loss of appetite
  • tiredness

Location

Cambridge
London

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 Hemant Kocher 
Dr David Propper

Supported by

Celgene Corporation
Medical Research Council (MRC)
NIHR Clinical Research Network: Cancer
Queen Mary University of London
Barts Health NHS Trust

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13611

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

Wendy took part in a new trial studying the possible side effect of hearing loss

A picture of Wendy

"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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