Cancer Research UK’s Drug Development Office has opened a trial of a new combination of drugs for the treatment of patients with brain cancer.
The Phase I clinical trial will take place at The Beatson West of Scotland Cancer Centre in Glasgow, the Christie Hospital in Manchester, and the Royal Marsden Hospital and The Institute of Cancer Research in Sutton. Patients with glioblastoma that has returned and requires surgery, will receive olaparib alongside temozolomide – standard chemotherapy treatment.
Olaparib is one of a new class of drugs called PARP inhibitors and is being developed by AstraZeneca. Glioblastoma is the most common and the most aggressive form of brain cancer.
The researchers hope to show that olaparib will make temozolomide more effective against brain tumour cells. Experiments in the laboratory have been promising but this will be the first time that the combination of olaparib and temozolomide has been trialled in patients.
The two-part trial will firstly determine if olaparib can reach brain tumours by crossing the blood-brain barrier. This structure protects the brain by separating brain fluids from the blood that is circulating around the rest of the body – but it can also stop some medicines from reaching their target.
Because the blood-brain barrier is disrupted in patients with glioblastoma, the researchers are optimistic that olaparib will reach the tumour cells.
In this initial part of the study, six patients will receive olaparib tablets for a few days leading up to their surgery. Tumour samples collected during surgery will be analysed to see if olaparib has crossed the blood-brain barrier and reached the tumour. In this part of the trial, olaparib will not provide any benefit as it will be given on its own, but the patients will then receive further standard treatment for their cancer after the surgery.
The second stage of the study will determine the appropriate doses for treatment combining olaparib and temozolomide, and may indicate whether the combination will be effective for some patients.
Lead clinician Professor Anthony Chalmers, of the University of Glasgow and the Beatson West of Scotland Cancer Centre, said: “It’s very exciting to launch a trial of a new approach to treat glioblastomas. Once the disease has returned, patients have limited options so there is an urgent need for new treatments.
“Most of the patients in the trial will have had previous treatment with radiotherapy and temozolomide and the likelihood of temozolomide being effective again is quite low. By adding olaparib we hope to increase the effectiveness of the temozolomide in treating tumours which have returned.”
Cancer Research UK led the development of temozolomide from early pioneering lab work to the discovery, development and first clinical trials of the drug in people with cancer. Temozolomide is approved for first-line treatment of brain cancers.
The charity also began some clinical trials of PARP inhibitors, which are a new type of drug for the treatment of cancer. These clinical trials were the result of more than a decade’s work by Cancer Research UK-funded scientists and others.
On their own, PARP inhibitors kill certain types of cancer cells by stopping their ability to repair gene faults. They are being used in clinical trials to treat patients with specific types of breast, ovarian and prostate cancers. PARP inhibitors can also be combined with existing cancer treatments such as chemotherapy and radiotherapy and it is hoped that this combination will be effective against a wider range of cancer types including brain tumours.
This latest trial is being funded and managed by the charity’s Drug Development Office (DDO).
Dr Nigel Blackburn, director of drug development at Cancer Research UK’s Drug Development Office, said: “It’s incredibly encouraging to launch this trial combining two drugs which have both been developed through work led by Cancer Research UK scientists. We hope that this new treatment approach will help extend the lives of brain cancer patients for whom the disease has returned.
“We’re heavily investing in further ways to develop targeted treatments through trials such as this to treat a wide range of cancers. We look forward to the results with great interest.”
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About PARP inhibitors
PARP inhibitors block PARP, a protein which is part of DNA’s ’emergency repair kit’ in cells – it prevents mistakes being passed on when cells grow and divide. An alternative ‘repair kit’ is also controlled by the BRCA1 and BRCA2 genes – these genes are faulty in some cancer cells.
When both copies of the BRCA1 or BRCA2 genes are faulty, the cells rely on the PARP pathway to repair damaged DNA. By blocking PARP with drugs, cancer cells which have lost BRCA1 or BRCA2 can no longer repair DNA damage and they die. This is why PARP inhibitors are effective in treating the small percentage of cancers in which BRCA1 or BRCA2 is faulty.
Because cancer treatments such as radiotherapy and chemotherapy kill cells by damaging DNA, PARP inhibitors also have the potential to increase the effectiveness of some of these treatments, even in cancers that do not have mutations in BRCA1 or BRCA2.
The charity’s commercial and development arm, Cancer Research Technology, first licensed the drug to industry for further trials that led to the approval of temozolomide.