Clinical Trials
If you are a patient and would like more information about clinical trials funded through the Cancer Vaccine Institute Click here.
The long term aim of all the trials funded by the CVI is to asses how well the vaccines work and how they can be further improved until an effective and safe vaccine is developed and becomes a standard treatment for a wide range of cancers. They may be used either alone or in addition to other treatments.
For each trial the patients will be monitored to see how their tumour responds to treatment and to ascertain whether there are any adverse effects of the treatment. Importantly, in order to determine the potency of the treatment, the immune response will be determined for each patient. It is hoped that the data accumulated by the end of each trial will show that patients can live longer or have delayed progression of their disease and that they have a better quality of life. Depending on the results of each of the trials the vaccines will either be ready for further, larger, randomized multi-centred trials or other variables will have been identified so that another similar trial can be conducted to further improve the vaccine.
Current Trials
Vaccine for Childhood Cancers
Osteosarcoma in children is rare, constituting only 5% of all childhood cancers. However, although improvements in chemotherapy have improved the outcome for this group of patients, relapse rates remain high and there remains a great need for alternative treatments in metastatic disease.
There is evidence from both human and mouse experiments that immunotherapy, and more specifically dendritic cell vaccines, might have an affect on these childhood cancers. Professor Dalgleish has already treated six children on an ‘informed consent’ basis who had all failed standard therapies using their own resected tumour as a vaccine. In one test patient there has been a dramatic clinical response to vaccination which constitutes a dramatic response rate among patients whose prognosis is otherwise poor.
Professor Dalgleish is collaborating with the Institute of Child Health on a two year phase I clinical trial to treat twenty patients with osteosarcoma followed later by other sarcoma types. The trial was peer reviewed through Cancer Research UK for funding at the ICH site and the CVI is providing co-funding for the work to be carried out at St George’s University of London. Recruitment at the ICH has started already and St George’s expects to begin recruitment by the beginning of 2009.
This will be the first trial of its kind in paediatric oncology. Patients will be treated with a course of about ten vaccinations of dendritic cells pulsed with autologous tumour lysate initially every two weeks but gradually dropping to every two months. It is hoped that this vaccine will stimulate an immune response against the tumour. To aid this process the patients will also be given a course of a drug called Interleukin-2 (IL-2) which has stimulatory effects on the immune response. The dose of IL-2 that will be used in this trial has minimal toxicity and is suitable for children.
Vaccine for Malignant Melanoma
The incidence of malignant melanoma is set to treble over the next thirty years making it the fastest increasing cancer in Britain (CRUK 2004). Unless the disease is caught early, there is currently no effective treatment available particularly in metastatic disease where chemotherapy often fails
In August 2007 a three year Phase I/II trial funded by the CVI to investigate the efficacy of treating thirty stage IV malignant melanoma patients who had failed chemotherapy, with a dendritic cell vaccine ended. Analysis of this trial is still underway to determine how well the vaccine has worked to stimulate immunity in these patients. Clinical results so far indicate that patients who have low volume disease and who are largely fit and well, apart from their tumour, have responded well to dendritic cell therapy giving longer survival times than those treated by other therapies. Even patients who have progressed through maximum chemotherapy have responded with stable disease. Responses were most marked in metastases of the lung. Patients reported minimal side effects (common side effects including transient and mild flu-like symptoms and tenderness at the site of vaccination) and an improvement in quality of life with an increase in appetite and subsequent weight gain.
Aldara / IL-2 Trial – Malignant Melanoma
A phase I clinical trial, funded by the CVI has recently finished which determined the efficacy of Aldara cream topically applied to cutaneous (on the surface) and sub-cutaneous (under the skin) melanoma lesions. In some cases the Aldara cream was applied in conjunction with injections of IL-2 into the melanoma lesion. Clinical results showed that Aldara treatment was effective in controlling the growth of about half of cutaneous melanoma lesions. The lessons learned from the Aldara trial will be applied to later studies, possibly in combination with other types of immunotherapy (see below).
Future Clinical Trials
A number of clinical trials to test vaccines and immunotherapeutic approaches have been proposed. Clinical trial protocols and vaccines are currently being organised and there are no starting dates for any of the following proposed trials. Details of future clinical trials will be updated regularly. Please return to this site in the near future for further details of new clinical trials and when they will start recruiting.
Zometa and IL-2
Previously published studies have demonstrated that a combination of Zometa (a drug given in metastatic disease) and IL-2 (an immuno-stimulatory agent) have synergy in prostate cancer. Our own observations suggest that sequential treatment with these drugs in melanoma may have some clinical benefit. Since Zometa is known to have immunological effects we intend to do a pilot study to look at the effect of this treatment on the activity of peripheral blood immune cells, principally gamma-delta T cells, in melanoma patients.
Vaccine for Malignant Melanoma
It is becoming clear that while some patients respond very well to vaccines, others do not. Further research is needed to pin down the best formulation of the vaccine and to identify who will respond and who is responding once treatment has begun. Using the data from the previous melanoma trial (see above) in combination with the recent laboratory research data on dendritic cell loading and maturation and possibly incorporating the biomarkers data from our laboratory research, a new more effective trial protocol will be developed.
The CVI has agreed to continue its funding for a new three year phase I/II melanoma trial anticipated to start in 2008 treating a further thirty patients . Decisions about the final combination of treatments awaits the outcome of trial one. However, it is expected that it will involve some of the following approaches: increasing the effectiveness of dendritic cells; removing regulatory cells that damp down immune responses; increasing the effectiveness of the T cells that kill cancers; and combining the vaccine with chemotherapy. It is becoming apparent that vaccines could work much better in combination with other standard treatments and observations support this with marked unexpected responses to chemotherapy, radiotherapy, anti-angiogenic and anti-inflammatory treatments. Use of vaccine in combination with chemotherapy at lower doses may also have fewer toxic side effects for patients.
Prostate Cancer Vaccine
In the UK 1 in 14 men will develop prostate cancer in their lifetime. Indeed, it is the most common form of cancer in men and is the second most common cause of death from cancer for men (Prostate Research Campaign UK). It is currently treated with radiotherapy and hormone therapy and if caught early enough surgery. However, patients that fail hormone therapy have little recourse to other treatment and there is a real need for other forms of intervention.
CVI’s long term financial support has allowed a number of studies to proceed on whole tumour cell vaccination. Out of this original work a small biotech company, Onyvax, was born which has successfully developed a whole cell vaccine to a phase IIb clinical trial for prostate cancer in patients that have failed hormone treatment.
The CVI has agreed to fund a further two year phase I/II trial to investigate ways to improve the efficacy of the Onyvax vaccine. Negotiations are ongoing with Onyvax to acquire the necessary vaccine and to determine the best possible combination of agents. The agents include cyclophosphamide (which inhibits T regulatory cells and so aids the stimulation of the immune response) and doxycycline (which inhibits matrix metalloproteases, a class of enzyme involved in various aspects of tumour progression). There is currently no other trial of this kind in prostate cancer.
Mycobacterium Vaccae (M vaccae) in Malignant Melanoma
Clinical trials have demonstrated the effectiveness of vaccination with M vaccae in the treatment of melanoma and lung cancer. M vaccae is similar to the bacterium that causes tuberculosis, but in this formulation (produced to clinical trial standard and heat killed) is completely safe for use in humans. The exact mechanism by which the treatment works is unclear but it is likely that there is a non-specific recognition of M vaccae which stimulates the relatively suppressed immune system in cancer patients to respond to tumour antigens. Production of this agent was previously halted by SR Pharma. However, the importance of this product is reflected by the financial support gathered from a single anonymous donation which has allowed production to continue.
The CVI has agreed to fund a two year phase I trial on thirty patients with malignant melanoma using M vaccae and where appropriate in combination with low dose IL-2. This initial trial will be done to batch test the SRL172TM for comparison with previous trials. However, unlike previous trials the aim is to follow immune responses in order to understand the underlying biology in these patients. There are currently no other trials of this kind being undertaken.
Brain Cancer Vaccine
In the UK 16,000 people are diagnosed with a brain tumour each year. It is the second most common cause of cancer mortality in the UK. Aside from primary tumours, 20% of all cancers go on to develop a secondary tumour in the brain. (Brain Research Trust 2007).
Reports in the scientific literature suggest that dendritic cell vaccines have clinical effects in the most common type of brain tumour, malignant glioma, with patients raising immune responses to the vaccines. There is also anecdotal data from Professor Dalgleish’s clinical work to suggest that dendritic cell vaccines give good control of the disease.
A European consortium headed by Professor van Gool, a specialist in DC vaccines for brain tumours, aims to undertake a three year Phase I/II clinical trial to treat over 100 brain tumour patients using dendritic cells pulsed with lysate prepared from autologous tumour cells. The CVI will provide the funding for the Professor Dalgleish but other members of this consortium are currently seeking funding for their contribution.
If you are a patient and would like more information about clinical trials funded through the Cancer Vaccine Institute please contact our research nurse on 020 8725 0147.
