A trial of atovaquone with chemotherapy and radiotherapy for non small cell lung cancer (ARCADIAN)
Cancer type:
Status:
Phase:
This trial looked at atovaquone with 
. It was for people with that had spread into the nearby tissue.
This trial was supported by Cancer Research UK. It was open for people to join between 2020 and 2022. The team analysed the results in 2024.
More about this trial
Cancer cells divide and grow quickly. Because of this, some areas in the cancer have very little oxygen. This can trigger a system in the cell which makes cancers grow and spread more quickly. It can also make cancers more difficult to treat with radiotherapy.
Atovaquone is used to prevent and treat certain infections. But research had shown that it can increase the amount of oxygen in cancer cells.
Doctors sometimes use chemotherapy and radiotherapy at the same time to treat non small cell lung cancer. This is called chemoradiotherapy.
Researchers hope that having atovaquone alongside chemoradiotherapy will work better than chemoradiotherapy alone. This trial was looking at it in people with non small cell lung cancer that had spread to nearby tissue.
The research team want to do a large trial to find out if this is the case. But they needed to do a small phase 1 trial first, to find out the best dose to give. This is a .
The main aims of this small trial were to:
- find the best dose of atovaquone to give with chemoradiotherapy
- learn about the side effects of giving atovaquone with chemoradiotherapy
Summary of results
The researchers found that atovaquone with chemoradiotherapy didn’t cause too many side effects. They also found the best dose to use for future trials.
Results
A total of 21 people joined this phase 1 trial. They were between 41 and 70 years old and had non small cell lung cancer (NSCLC).
Everyone had the same treatment:
- radiotherapy every day (Monday to Friday) for 6 ½ weeks
- cisplatin chemotherapy twice during radiotherapy (weeks 1 and 4)
- vinorelbine chemotherapy 4 times during radiotherapy (weeks 1, 2, 4 and 5)
- atovaquone as a liquid (suspension) to swallow twice a day, from 3 weeks before until they finished radiotherapy
The first few people had the lowest dose of atovaquone. They didn’t have any serious side effects, so the next few people had a higher dose. And so on. This is called dose escalation. There were 4 dose levels in total.
The trial team decided that dose level 4 was the best one to use in future trials.
Side effects
Everyone taking part had at least one side effect from treatment. Many of them were mild or didn’t last long. But some people did have a more severe side effect.
Some of the side effects were caused by radiotherapy or chemotherapy rather than atovaquone.
The most common side effects were:
- extreme tiredness (fatigue)
- constipation or diarrhoea
- inflammation of the oesophagus (food pipe) called oesophagitis
- feeling sick
There were 15 people in group 4 who had the highest dose. Only 1 person had side effects that suggested the dose of atovaquone was too high. This is called a dose limiting toxicity. The side effects they had were an inflamed oesophagus (oesophagitis) and feeling sick.
We have more information about the side effects of chemoradiotherapy in our Lung cancer section.
Oxygen level in cells
The team used a special scan to measure the oxygen level in cancer cells before and after atovaquone treatment. They were able to do this for 12 people.
The results showed that the oxygen level increased after taking atovaquone in 9 of these 12 people.
How well treatment worked
The trial team were able to look at how well atovaquone given with chemoradiotherapy worked in 19 people who took part.
They found that the cancer had:
- gone away in 1 person
- got a bit smaller in 13 people
- stayed the same in 3 people
- got worse in 2 people
These results are at least as good as you might expect from chemoradiotherapy alone.
Conclusion
The trial team concluded that they found the best dose of atovaquone to give alongside chemoradiotherapy. And that it didn’t cause too many side effects.
They suggest more trials are done to find out more about how well it works. This could include trials for cancers other than lung cancer.
Where this information comes from
We have based this summary on the information in the articles below. We have not analysed the data ourselves.
As far as we are aware, the results have not been reviewed by independent specialists () or published in a medical journal yet. The team hope to publish the full results in the future.
The lay summary we link to here has been written by the trial team.
Atovaquone with Radical ChemorADIotherapy in locally Advanced NSCLC – LAY SUMMARY
University of Oxford website. Accessed April 2025.
A Phase I Trial of the Hypoxia Modifier Atovaquone in Combination with Radical Concurrent Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer – Statistics report.
Maggie Qiao and others
Version 2.0, February 2025.
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.
Chief Investigator
Professor Geoff Higgins
Supported by
Cancer Research UK
University of Oxford
MRC Oxford Institute for Radiation Oncology
Cancer Research UK Oxford Centre
Oncology Clinical Trials Office (OCTO) Oxford
Oxford Clinical Trials Research Unit (OCTRU)
Other information
This is Cancer Research UK trial number CRUK/18/015.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
