Research Studies

Here you will find the latest updates on the ongoing research being carried out at Mount Vernon Cancer Centre which the CTRT has helped to support.

Blood Vessels

PROGRESS IN DEVELOPING DRUGS THAT TARGET TUMOUR BLOOD VESSELS

For tumours to grow larger than a few millimetres in size, it is necessary for them to develop their own blood supply. There are two fundamentally different approaches to targeting blood vessels that supply tumours. The approach that is most developed is aimed at preventing new tumour blood vessels from growing and is called anti-angiogenesis. Several drugs such as bevacizumab and sunitanib and pazopanib are already licensed for use in different tumours. The other approach uses drugs, called vascular disruptive agents, to selectively damage the blood vessels already supplying cancers so that the blood flow to the cancer can be stopped and the cancers rapidly die.

The CTRT has made a major contribution into funding trials of vascular disruptive agents, commonly known as VDA’s. In the 1990’s it supported trials of vadimezan (also known as DMXAA and AS1404) which was developed in New Zealand. The original first in man phase I trials were carried out at Mount Vernon Hospital, Bradford Royal Infirmary and in Auckland, New Zealand organised by Cancer Research UK. Early results suggest that it could reduce blood supply to tumours in some patients. This drug was licensed to Antisoma and then Novartis organised world-wide clinical trials. Unfortunately these trials did not show that this drug was as effective as was initially expected.

The CTRT in collaboration with CRUK then ran clinical trials of fosbretabulin (also known as combretastatin A4 phosphate -CA4P) and then trials of OXI4503. These trials used special MRI scans to show that these drugs could shut down the blood supply to human cancers within a few hours. The initial trials showed that these drugs had unusual side effects, such as raising blood pressure and causing acute pain in cancers, presumably due to the lack of oxygen. Although OXI4503 appeared the most powerful it was considered rather toxic, so we are continuing development with fosbretabulin.
Laboratory studies showed that these drugs work best when given in combination with cytotoxic drugs or radiotherapy. This led to combination trials being run at Mount Vernon Hospital and supported by CTRT. More recently it has been shown that certain drugs that target VEGF can prevent the re-growth of viable cells that survive the initial VDA therapy. This has led Professor Rustin to propose trials that combine VDA therapy with anti-angiogenic agents. A trial of fosbretabulin combined with pazopanib started in October 2014 for patients with relapsed ovarian cancer at Mount Vernon, Royal Marsden and Christie Hospitals. After treating the first 12 patients it was clear that the combination of drugs is active and it was possible to select the correct dose for a randomised trial. This started in 10 UK centres in 2016, but was stopped after recruiting 21 patients. Although there was obvious anti-tumour effect with the combination there were three reversible cardiac events. This unfortunately led to Novartis who supplied the pazopanib to close the trial. The CTRT remains committed to fund the translational research associated with this trial as well as the research staff working on this trial at Mount Vernon.

Ovarian Cancer Research

Progress: The Cancer Treatment and Research Trust enabled Mount Vernon Cancer Centre over the past 20 years to enter a larger proportion of patients with ovarian cancer into clinical trials than all but a few centres in Europe. Generous donations have funded a dedicated group of research nurses and data managers who work closely with Professor Gordon Rustin, Dr Marcia Hall, and the junior doctors to look after the patients and collect all the important data so new treatments can be introduced and closely analysed.

Melanoma Research

CTRT support is essential to allow us to run a comprehensive program of clinical trials for patients with melanoma and renal cancer. This allows our patients access to the most modern treatments. The research team is led by Dr. Paul Nathan (melanoma and renal cancer), Dr Heather Shaw (melanoma) and Dr Anand Sharma (renal cancer). Our two full time research nurses (Ange Smith and Simona Linwood) and three study coordinators Christiana Groutides, Jabir Merali and Rowena Sahabandu run all aspects of clinical trials from patient care to data management. 80% of their salaries are covered by charitable funds and commercial trial income, only one salary is received from the national cancer research network. Our patients therefore have access to the most innovative treatments because of the generosity of contributors to CTRT.

Donations to CTRT that stipulate use for the melanoma and renal teams will only be used to support research in the areas the donor desires.

Melanoma

 CTRT supports a research session for Dr.Veronique Bataille, a consultant dermatologist who has a major scientific interest in the genetics of melanoma and predisposing factors of the disease. The influence of the gut microbiome on outcome in patients receivingimmunotherapy is an area of significant major international interest. We are part of acollaborative group headed by Prof Tim Spector at Kings College that has attracted funding toinvestigate the impact of gut microbial diversity on outcome in melanoma patients receiving mmunotherapy.

We have appointed a research fellow, Dr Karla Lee, to help deliver the project. Dr Lee has registered for a PhD at Kings College and is half- funded by CTRT for a 3 year period
starting September 2018. Dr Bataille has led the development of the microbiome project. PRIMM, a biomarker sub-study of the project, has been adopted onto the NCRN national portfolio. leads research projects on skin phenotype in patients with high risk and metastatic melanoma and a second project analysing the association of the microbiome (gut bacteria) with clinical outcome in melanoma. CTRT have also provided a grant to enable our outgoing research fellow, Dr.Romaana Mir, to perform an analysis of the clinical impact of surveillance scanning in high risk melanoma and audit outcomes for patients with brain metastases treated with stereotactic radiotherapy. Both studies have been submitted for publication.

Renal Cancer

Our renal cancer clinical trial portfolio continues to grow. Patients now have the opportunity to access clinical trials in the adjuvant (following surgery) and advanced disease settings. Many of our studies are attempting to identify improved ways to stimulate an effective immune response to the cancer in an attempt to gain long term control of the disease. Dr Sharma is lead investigator on a novel treatment that looks to disrupt the metabolism of renal cancer cells.

Testicular Cancer Research

Testicular Cancer

The value of research is particularly well demonstrated by the great progress made in curing testicular cancer. 30 years ago, less that 10% of patients survived once their cancer had spread. Now over 90% are cured. Over half of all patients are found to have stage 1 disease with no evidence of spread from the testicle. The majority of these stage 1 patients are managed by close surveillance and most of these patients avoid the need for chemotherapy or radiotherapy. However about a fifth of all patients on surveillance will relapse, but are then cured by chemotherapy. Thanks to a database managed by funding from the CTRT we can reassure patients with the following data: Professor Rustin has managed over 1600 patients with stage 1 testicular cancer and only 4 patients have died from that cancer, including two who had refused to attend follow-up appointments.