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 cancer vaccines or cancer immunotherapy works and how they can be further improved until an effective and safe treatment is developed and becomes a standard 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
There are no trials currently running for cancer immunotherapy at SGUL/St George's Hospital. However the following trial, which is ongoing at the Institute of Child Health and Great Ormond Street Hospital results from work initially done at SGUL with funding from the CVI to do a limited number of patients "off-trial" to provide proof of principle for the efficacy of this treatment.
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. Until recently it was the intention of the CVI to fund an extention of this trial at the St George's site. However, plans for facilities to generate dendritic cell vaccines at St George's have been delayed making their contribution towards this trial impossible. We are now considering whether funding can be provided for the ICH study, which is expanding the number of patients on the trial,or for other vaccine related paediatric studies. Updates will be provided on this site when further details are known.
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. The trial closed in 2009 and work continues to evaluate the immune response of the patients treated with DC vaccines.
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 (Green 2007). Since the publication of this clinical work we have looked at the immunological outcome of this treatment. We find that there are significant systemic immunological changes in Aldara/IL-2 treated patients. A scientific paper describing this work has been published in the British Journal of Dermatology (Green 2008). There are reports that this approach has been adopted as a preferred treatment throughout the country and it is routinely used in our own clinics at St Georges. The member of staff, employed to do this work, has recently received her qualification of M.D. based on this research.
We have begun to consider the next logical step to develop this knowledge and are collaborating with Systems Biology Group (a small Oxford R&D company) to develop a new treatment for melanoma (see future work, 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.
A study of Zometa and IL-2 as immune modulators in advanced melanoma
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 immune cells in the blood, principally gamma-delta T cells, in melanoma patients.
Hiltonol and IL-2 for the treatment of cutaneous melanoma.
Following the success of the Aldara/interleukin-2 study, we have been discussing the use of Hiltonol, a drug which has similar, but different, immunomodulatory properties to Aldara (see above). The protocol for this trial is currently under discussion and funding is dependent on approval by our Advisory Board.
Studies to determine the immunological effects of radiotherapy.
Evidence has been documented for a potential synergy between immunotherapy and radiotherapy. However, there is a lack of studies to determine the parameters for effective radiotherapy in combination with immunotherapy. The CVI has agreed to fund basic research and an observational clinical trial suggested by Prof Malcolm Mason in Cardiff. This project has received the support of the Wales Cancer Trials Unit and protocols are currently being written for submission to the appropriate regulatory authorities.
Other potential clinical trials
Although it has sadly become difficult to continue making dendritic cell vaccines at SGUL, Prof Dalgleish is in discussion with colleages in Germany to organise collaborations for future trials. In addition Prof Dalgleish maintains an interest in mycobacteria for cancer immunotherapy. Bacterial preparations such as BCG and Mycobacterium vaccae have shown promise for the treatment of some cancer. Thus a collaboration with is under consideration with a new biotech company (Immmodulon). This company was set up to investigate the use of a new mycobacterial variant as an immune modulating agent and is expected to being early phase clincal trials in melanoma early in 2010. Success of the phase I trials may make this product availble for further academic work.
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.
