A trial of a PARP inhibitor called AG014699 and temozolomide for advanced cancer

Cancer type:

All cancer types




Phase 1

This trial was looking at a combination of AG014699 and temozolomide for advanced cancer. This trial was supported by Cancer Research UK.

Doctors often treat advanced cancer Open a glossary item with chemotherapy. The aim of chemotherapy is to damage and kill cancer cells. But some cancer cells can repair themselves, and this is partly why chemotherapy does not always work very well for some types of cancer.

PARP is an enzyme Open a glossary item that helps damaged cells to repair themselves. PARP stands for ‘poly (ADP-ribose) polymerase’. Doctors hoped that if they could stop PARP working, cancer cells would not be able to repair themselves after chemotherapy. By doing this, they hoped to make the chemotherapy work better.

This trial was looking at a treatment called a PARP inhibitor, which blocks PARP. The PARP inhibitor they used was called AG014699. They were testing it in combination with a chemotherapy drug called temozolomide.

The trial was in 2 parts. The first part was for people with different types of solid tumours Open a glossary item. The second part of the trial was for people with melanoma.

The main aims of the trial were to

  • Find the best doses of temozolomide and AG014699 to have together
  • Learn more about how AG014699 worked and what the side effects were
  • See how well the combination of temozolomide and AG014699 worked

Summary of results

The trial team worked out safe doses of AG014699 and temozolomide that could be used together. And they found that cancer responded to this drug combination in about 1 in 10 people (10%) in this trial.

In the first part of the trial, the people taking part had a range of solid tumours. Everybody had a low dose of temozolomide. The first few people also had a low dose of AG014699. As they didn’t have any serious side effects, the next few people had a higher dose of AG014699 and so on. In this way, the researchers found the highest dose of AG014699 that they could give safely with temozolomide.

In the second part of the trial, the people taking part all had melanoma. Everybody had the highest safe dose of AG014699 that had been worked out in part 1. This time, the researchers slowly increased the dose of temozolomide. By doing this, they found the highest doses of both drugs that could be used together, without causing too many side effects.

The side effects that people did have included a drop in the number of blood cells, tiredness (fatigue), sickness, heartburn, constipation, diarrhoea and headache.

  • 32 people had treatment as part of this trial
  • In 1 person who had melanoma, the cancer disappeared completely – researchers call this a complete response Open a glossary item. And after more than a year and a half, it had not started growing again
  • In 2 people, the cancer had got smaller – researchers call this a partial response Open a glossary item
  • In 10 people, the cancer had stayed the same size – researchers call this stable disease Open a glossary item
  • In 16 people, the cancer had got bigger
  • The researchers didn’t have results for 3 people

The trial team learnt more about how AG014699 worked, and found that having the 2 drugs together helped some people in this trial. They suggest this should be looked at in further clinical trials involving more people.

We have based this summary on information from the team who ran the trial. As far as we are aware, the information they sent us has not been reviewed independently (peer reviewed Open a glossary item) or published in a medical journal yet. The figures we quote above were provided by the trial team. We have not analysed the data ourselves.

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 H Calvert

Supported by

Cancer Research UK (Centre for Drug Development)

Other information

This is Cancer Research UK trial number CRUKD/03/042.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle - 345

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

Cara took part in a clinical trial

A picture of Cara

"I am glad that taking part in a trial might help others on their own cancer journey.”

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