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.
PARP inhibitors including olaparib are a new type of personalised medicine that work by turning a tumour’s specific genetic defect against itself. These drugs are based on experiments conducted at the ICR and funded by Cancer Research UK and Breakthrough Breast Cancer.
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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Notes to editors:
*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.
Cancer Research UK’s Beatson Institute for Cancer Research
As one of Cancer Research UK’s core-funded institutes the Beatson Institute carries out a programme of world-class science directed at understanding key aspects of cancer cell behavious, and try to translate these discoveries into new therapies and diagnostic/prognostic tools to help cancer patients. The Institute benefits from close interactions with the University of Glasgow, including strong links with the University’s Institute of Cancer Sciences.
Cancer Research UK’s Drug Development Office
Cancer Research UK has an impressive record of developing novel treatments for cancer. It currently has a portfolio of around 36 new anti-cancer agents in preclinical development, phase I or early phase II clinical trials. Since 1982, the Cancer Research UK Drug Development Office has taken over 100 potential new anti-cancer agents into clinical trials in patients, five of which have made it to market and many others are still in clinical development. These include Temozolomide, a drug discovered by Cancer Research UK scientists, that is an effective new treatment for brain cancer. Six other drugs are in late development phase III trials. This rate of success is comparable to that of any pharmaceutical company.
Cancer Research UK
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.
For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
- The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.
For more information visit www.icr.ac.uk
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.
Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.
Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
For more information, visit www.royalmarsden.nhs.uk