A phase 1 trial looking at olaparib with chemotherapy and radiotherapy (chemoradiotherapy) for people with locally advanced pancreatic cancer (PIONEER)
Full title: PIONEER: A Phase I Study of Olaparib in Combination with Chemo-radiation in Locally Advanced Pancreatic Cancer
Why is this trial being carried out?
Pancreatic cancer that has started growing into organs or blood vessels around the pancreas, meaning it is not possible to remove the cancer with surgery, is called locally advanced pancreatic cancer. People with this type of cancer are sometimes offered chemotherapy combined with radiotherapy. This treatment is called chemoradiotherapy.
Olaparib is an experimental cancer drug called a PARP-1 inhibitor that stops an enzyme called PARP-1 from working. The PARP-1 enzyme is used by healthy cells to repair DNA damage.
Cancer cells also use PARP-1 to repair the DNA damage that happens when they come under attack, for example after chemotherapy or radiotherapy treatment. So when olaparib is used to stop PARP-1 working, cancer cells can no longer repair themselves and die. Olaparib may help to control the cancer and make chemotherapy and radiotherapy treatments work better.
The PIONEER trial wants to find out the highest dose of olaparib that is safe to give with chemoradiotherapy. The researchers also want to learn more about the side effects of combining olaparib with chemoradiotherapy.
Locally advanced pancreatic cancer has started growing outside the pancreas, into nearby large blood vessels and possibly into the lymph nodes. But it has not spread to other areas of the body. Doctors can treat people with locally advanced pancreatic cancer with a combination of chemotherapy using the drug capecitabine and radiotherapy. This is called chemoradiation.
Olaparib is a type of biological therapy called a PARP-1 inhibitor. It stops an enzyme called PARP-1 from working. This enzyme helps to repair the DNA in cells when it is damaged. DNA controls growth, development and how the body works. Cancer cells have damaged DNA and rely on PARP to repair them. So when olaparib stops PARP from repairing DNA damage, the cancer cells die.
Radiotherapy and some chemotherapy drugs damage DNA in cancer cells and kills them. Doctors think having olaparib along with chemotherapy and radiotherapy will make these treatments work better.
In this trial doctors want to
- Find the highest safest dose of olaparib to give with chemoradioation
- Learn more about the side effects of olaparib with chemoradiation
Who is the trial suitable for?
The PIONEER trial may be suitable for you if you:
- have locally advanced inoperable pancreatic ductal adenocarcinoma cancer
- have completed a first round of chemotherapy and the cancer has not spread during treatment
- are fit and well enough to have the treatment – tests will be done to check this.
It is not suitable for you if you:
- have pancreatic cancer that has spread to another part of the body (advanced or metastatic cancer)
- have taken part in another clinical trial for a new treatment in the last 12 months
- have had previous treatment with a PARP inhibitor, including olaparib
- have had blood transfusions in the last month
- have had major surgery in the last two weeks
- have any problems with your digestive system that could affect how you absorb the drug
- have myelodysplastic syndrome or acute myeloid leukaemia
- have a heart condition that’s not well controlled by medication
- have uncontrolled seizures
- are HIV, Hepatitis B or Hepatitis C positive.
There may be other reasons for not being able to take part in a trial. It is important to speak to your consultant about whether this trial might be suitable for you.
Recruitment start date: July 2015
Recruitment end date: April 2019
Published April 2016
Review date February 2018
The PIONEER trial is being carried out at:
Belfast City Hospital
Guy’s and St Thomas'
The Beatson West of Scotland Cancer Centre, Glasgow
Professor Jeff Evans
You can contact the trial centre coordinator:
Doctor Liz-Anne Lewsley, CR-UK Clinical Trials Unit, Beatson West of Scotland Cancer Centre, University of Glasgow
Telephone: 0141 301 7193
How to join a trial
Please speak to your consultant about whether this trial is suitable for you.
If you have any questions about pancreatic cancer you can speak to one of our specialist nurses on our Support Line.
How to find out more
For further information about this trial please visit the UK Clinical Trials Gateway website.
For references used to develop this information please email us.