Here you will find the latest updates on the ongoing research being carried out at Mount Vernon Cancer Centre and at West London Cancer Centre, Charing Cross Hospital which CTRT has helped to support.
You can also view publications, presentations and full research reports.
Research Updates
Click on a research area or 'more details' to show/hide full research updates:
Breast cancer Research at the Mount Vernon Cancer Centre
At the Mount Vernon Cancer Centre we have a very active Breast Cancer Research Team who have been working hard to improve our understanding of how breast cancers develop, improving diagnosis and developing better and more effective treatments. We have developed national and international collaborations over the last decade to assist with our research programme and also work very closely with the other hospitals in the Mount Vernon Network to improve access to clinical trials to all the patients in our area.
The Breast Cancer Research Team run 15-20 clinical trials at any one time at the Cancer Centre which offer our patients the opportunity to have access to the latest treatments options. In recent years we have taken part in the large multi-centre trials that have established the role of new hormone therapies (the aromatase inhibitors), new chemotherapy agents and schedules and targeted therapies such as herceptin and avastin. More recently we have been a leading research centre for the development of new treatments when herceptin stops working with trials using lapatinib and pertuzumab.
We have an internationally recognised interest in developing better ways of predicting which patients will benefit from individual therapies so as to spare those who will not respond unnecessary toxicity. In a major trial between the Mount Vernon Cancer Centre and Baylor College, Houston, USA, we are using some of the latest diagnostic technologies, DNA microarrays, to predict response to individual chemotherapy drugs.
We are a leading research centre, in collaboration with the Paul Strickland Scanner Centre, in using advanced imaging technologies such as DCE-MRI and PET scans, to better understand how tumours respond to drug treatments and selecting patients who will respond to treatment early in the course of treatment and several weeks before tumour shrinkage occurs.
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. Mount Vernon Cancer Centre has been one of the largest recruiters into trials that have shown that patients who are found to have cancer just localised to the testicle can be managed by close surveillance. When patients present to the cancer centre after having their cancer containing testicle removed, they have scans and blood tests to see if it has spread. Over half of all patients are found to have stage 1 disease with no evidence of spread. Professor Gordon Rustin was the international chief investigator of a trial that has investigated the best way to follow these patients. This trial has shown that close surveillance is safe as despite 17% of the 414 patients relapsing all who relapsed were then cured by chemotherapy and in some cases additional surgery. This trial showed that it is safe to cut down the number of CT scans thus reducing the radiation dose to these patients.
A trial is soon to start investigating the role of magnetic resonance imaging (MRI) scans in patients on surveillance to see if this could further cut down the dose of radiation.
KIDNEY CANCER & MELANOMA
CTRT support has enabled us to run a comprehensive program of clinical trials for patients with kidney cancer and melanoma. This allows access to the most modern treatments for our patients.
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During the last year we have recruited patients into the following clinical studies:
Melanoma:
- EORTC 18961 GM2 vaccine for high risk melanoma
- EORTC 18032 Dacarbazine vs. Extended Dose Temozolamide in stage IV melanoma
- Dacarbazine + BAY 43-9006 in stage IV melanoma
Kidney Cancer
- RE04 Interferon vs. Interferon, Il-2 and 5-FU in metastatic kidney cancer
- BAY 43-9006 vs. placebo in 2nd line treatment of metastatic kidney cancer
- SU011248 vs interferon in 1st line treatment of metastatic kidney cancer Zoledronate in metastatic kidney cancer
Further studies with vaccines for resected stage III and IV melanoma are expected to open before the end of 2005.
We have active translational research programmes in both diseases.
In collaboration with Dr. Hugh Montgomery (UCL) we are examining the role of single nucleotide polymorphisms in kidney cancer in an attempt to understand whether differences in the genetic background of individuals contributes to their risk of developing kidney cancer.
In collaboration with Dr. Steve Everett at the Gray Cancer Institute and Dr. Claire Ling at the RAFT research institute we are examining the expression of extra-hepatic cytochromes in melanoma as potential targets for therapeutic prodrugs.
Ovarian Cancer
Progress: The Cancer Treatment and Research Trust has enabled Mount Vernon Cancer Centre to enter more patients with ovarian cancer into clinical trials than almost any centre 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. Our work has been recognised by Professor Rustin being made Chairman of the Ovarian Cancer Subgroup of the National Cancer Research Institute Gynaecological Clinical Studies Group, which is succeeding in producing a portfolio of clinical trials for ovarian cancer patients that is at the forefront of ovarian cancer research worldwide.
Through analysis of thousands of patients in clinical trials around the world, we have developed new ways of detecting and monitoring ovarian cancer based on changes in levels of CA125 – a chemical present in the blood of patients with ovarian cancer. These tests also provide an early indication of patients’ responses to different treatments. Our definitions, based on changes in CA 125 levels (now widely known as the “Rustin” criteria), have now been accepted by all major trial groups around the world. And the US Food and Drug Administration are considering accepting them for regulatory use.
We are also using CA 125 tests to assess new drugs which are relatively non-toxic and work by controlling rather than killing cancers.
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Current clinical trials: For patients who present with ovarian cancer that has spread we have several trials that are trying to find the best chemotherapy. By June 2006 we had entered 42 patients into the SCOTROC 4 trial, which is being run by the Scottish Cancer Trials Group. This trial is trying to find out the best way of giving carboplatin which is the most active drug against ovarian cancer. We are about to start entering patients into the ICON 7 trial, which will determine whether patients might benefit from the addition of the drug bevacuzamib (Avastin), which targets cancer blood vessels. We will also soon be starting a trial to determine whether a tablet drug called erlotinib (Tarceva) can benefit patients.
There are many trials either up and running or in planning for patients who have relapsed. Professor Rustin is the principal investigator of two trials for patients whose cancer has recurred within 6 months of finishing the previous chemotherapy. In one, patients receive a drug called combretastatin (CA4P) that attacks the blood vessels supplying cancers. Twenty hours later they receive paclitaxel and carboplatin. After laboratory studies had shown that the three drugs together are particularly active, we carried out a study in 46 patients to find out the best dose of these three drugs. In another trial we are trying to find out if a new drug known as ZK219477 can shrink ovarian cancer.
We are the first centre to enter patients into a trial to see if an oral drug called BIBF 1120 can prevent patients relapsing. This drug attacks several pathways essential for ovarian cancer spread including blood vessel growth. We will soon be starting trials looking at other agents that target particular pathways involved in cancer development as well as trying to overcome resistance to currently available drugs.
CA 125: This is a chemical measured in the blood that is elevated in most patients with ovarian cancer. The level of CA 125 can rise months prior to a patient developing any symptoms from their cancer. Professor Rustin is the principal investigator and entered 150 patients into the OVO5 trial, which is investigating whether early treatment of relapsed ovarian cancer detected just by rising levels of CA 125, is better than delaying treatment until patients develop symptoms suggesting relapse. The results of this trial should be available in 2008. Professor Rustin and his team have managed to analyse data on thousands of patients entering clinical trials around the world. They discovered that it is possible to use serial CA 125 measurements to show whether ovarian cancer is responding to treatment or not. Changes in CA 125 are quicker and more accurate than other methods for following patient’s progress. We have produced definitions based on changes in CA 125 levels, that have now been accepted by all major trial groups around the world. This has lead to the US Food and Drug Administration to look into accepting them for regulatory use. The data managers involved in this work have been funded by the CTRT for several years and are still working on using them to discover new cancer treatments.
An example of this is the “CA 125 doubling trial”. We are looking at how quickly the CA 125 levels rise in patients who are having it measured every month after completing treatment for relapsed ovarian cancer. If levels rise to a certain level patients start the tablet tamoxifen to see if it will alter the rate at which CA 125 levels rise. Although the rising CA 125 levels indicate that the cancer is relapsing these patients can remain well for a long time. The ultimate aim of this trial is to see if well tolerated drugs such as tamoxifen can change the rate of rise of CA 125 levels, which would be an early indicator that a drug could delay or even prevent the regrowth of ovarian cancer. There are many drugs in development that could slow the growth of cancers and this approach could speed up the process of finding which are the best drugs for ovarian cancer patients.Back to top
Full Reports & Presentations
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Progress in developing drugs that target tumour blood vessels
Progress report on trials of combretastatin A4 Phosphate (CA4P), Dimethyl Xanthenone Acetic Acid (DMXAA) and OXi4503.
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. Several drugs, called vascular disruptive agents, are being developed with the aim of selectively damaging the blood vessels that supply cancers so that the blood flow to the cancer can be stopped. This should result in considerable damage to the tumour and if there is sufficient blood flow reduction, it is hoped that the tumours could be controlled.
Combretastatin
Combretastatin (CA4P) has been shown in the laboratory to shut down the blood supply to tumours. It is one of the first vascular targeting drugs to be tested in patients. This drug was originally isolated from the African Bush Willow. The first studies in patients with this drug were aimed at finding out whether it can be safely given to patients, what side effects it produces and whether it can actually shut down the blood supply to human tumours. Fewer than 200 cancer patients have so far received CA4P.
Cancer Research UK organised a trial in the United Kingdom with two participating hospitals; at the Mount Vernon Hospital, co-ordinated by Professor Rustin (pictured left), and at the Hammersmith Hospital, co-ordinated by Professor Price. In this trial patients received one dose of CA4P weekly. This trial was completed in December 2000. There are three trials which have been completed in the United States: one at Ireland Cancer Centre, Case Western University, Cleveland, where patients received the drug once every 3 weeks, and at Presbyterian Medical Centre, University of Pennsylvania, Philadelphia, where they received it daily for 5 days, and a small trial was carried out by Bristol Myers Squibb whilst they temporarily licensed the drug.
The trial performed in the United Kingdom, required that all patients had special scans performed to find out whether the blood flow through their tumour was being reduced by CA4P. Results of the special MRI scans performed on patients at Mount Vernon Hospital, indicated that CA4P can indeed reduce the blood flow to some human tumours. This was confirmed by PET scans performed at the Hammersmith Hospital and also in a small study performed in Boston. Although this is very exciting news, early results seem to indicate that this reduction in blood flow is not great enough in most patients to cause tumour shrinkage alone. This fits in with the work done at the Gray Cancer Institute which suggested that CA4P was far more effective when it was given with other drugs.
A small trial of combining Combretastatin with Carboplatin has been completed at Presbyterian Medical Centre, University of Pennsylvania, Philadelphia. This trial has helped in the design of a new phase Ib / II trial which started in June 2003 at Mount Vernon Hospital and more recently in Oxford and Detroit. By April 2005, 30 patients had enrolled in the Phase I arm of the study, in which clinicians assessed the safety and tolerability of combining CA4P with either carboplatin or paclitaxel or both drugs. The doublet combination has been well tolerated so far, and assessment of the triplet combination in at least 12 further patients is due to start in May 2005. The Phase II arm, which is expected to include between 14 and 30 patients will focus on collecting additional safety data and evaluating anti-tumour efficacy of the triple combination in women with platinum-resistant ovarian cancer.
A trial combining CA4P with radiotherapy started in 2003 just for patients who are suitable for receiving radiotherapy for cancers of the lung, head and neck, or prostate under the supervision of Professor Hoskin at Mount Vernon Hospital. A trial of CA4P combined with a radiolabelled antibody to an antigen on colon cancer also started in October 2003.
Selecting patients for trials of CA4P
There are very tight rules for selecting patients for these trials. We can only treat patients for whom there is no standard therapy. Many such patients are ill and we discourage patients travelling more than 1 hour from their home from entering our trials. More information about CA4P can be found on the Oxigene Inc website: www.oxigene.com.
DMXAA
DMXAA (AS1404) is another drug that attacks tumour blood vessels but works in a different way to CA4P. This drug, which was developed in New Zealand, had phase I trials carried out at Mount Vernon Hospital, Bradford Royal Infirmary and in Auckland, New Zealand organised by Cancer Research UK. Early results suggest that it too can reduce blood supply to tumours in some patients. Laboratory tests suggest that DMXAA will require to be given in combination with other drugs to cause major tumour shrinkage. This drug is now licensed to Antisoma who announced in March 2004 the successful completion of phase I trials and have proceeded on to a phase II study of DMXAA with carboplatin and paclitaxel in non-small cell lung cancer which started in September 2004. The first efficacy findings from this study are expected during the second half of 2005. Additional combination studies are also planned for ovarian and prostate cancers. At present no drug will be available outside the trials in New Zealand.
OXi4503
A CR-UK phase I trial of a new vascular disruptive agent called OXi4503 will start in May 2005 at Mount Vernon Hospital and the Christie Hospital, Manchester. Laboratory evaluation of OXi4503 has shown it to be more potent than CA4P and DMXAA, and capable of shrinking tumours when given alone. Again special MRI and PET scans will be performed to help evaluate the effects of OXi4503. A total of 18-40 patients will be entered into the study.
Selecting patients for trial of Oxi4503
There are very tight rules for selecting patients to receive OXi4503. We can only treat patients for whom there is no other standard therapy. All patients must have lumps of tumour that are larger than 2cm and can have measurements of blood flow by MRI at Mount Vernon or PET in Manchester. We discourage patients travelling more than 1 hour from their home from entering the trial because we are so concerned about ill patients not being able to cope with the rigors of this trial far from home. More details of this trial are available on the Cancer Research UK patient information website: www.cancerhelp.org.uk
The work on vascular disruptive agents is dependent upon close collaboration with the Gray Cancer Institute, the Paul Strickland Scanner Centre and Mount Vernon Hospital. It is dependent upon the support of Cancer Research UK, the National Lottery Charities Board, the Cancer Treatment and Research Trust and Oxigene Inc (USA).
