Mr Clive Stubbs and Dr Steve Johnson
Hello and welcome to the first contribution to this blog from The Cancer Research UK Clinical Trials Unit (CRCTU), which forms part of the School of Cancer Sciences at the University. Over the next five days we are going to share with you some of the exciting clinical research being done at the unit. We will also be touching on related topical events throughout the week.
The CRCTU is one of the largest cancer trials units in the UK and has been in existence for more than 30 years. We are one of three trials units at the University that form the Birmingham Centre for Clinical Trials and also form an integral part of the Birmingham Experimental Cancer Medicine Centre. The unit receives core funding from Cancer Research UK.
We specialise in the design, conduct and analysis of all phases of trials, from phase I, largely concerned with the safety of treatments, all the way through to phase IV cancer clinical trials, looking at the long term risks and benefits of treatments.We work with a wide range of investigators nationwide and internationally in a number of specialist areas including Breast cancer, Lung cancer, Paediatric cancer, Skin cancer and Urological cancer.
The CRCTU has experience in trials involving pharmaceutically active substances, the testing of new treatments on human subjects for the first time, radiotherapy, devices, surgery, allogeneic stem cell transplantation, gene therapy, immunotherapy and biomarker discovery and development.
With this week being international men’s health week, we thought it fitting to focus on two prostate cancer trials that are the product of our unit, one that has closed to recruitment and one that began recruiting patients just over a year ago.
Prostate cancer is by far the most common cancer in men (excluding non-melanoma skin cancer), accounting for one in four cases. In 2011 in the UK, over 41,000 men were diagnosed with the disease. Whilst being relatively indolent, with most men dying with prostate cancer rather than because of it, almost 11,000 men died from their prostate cancer in 2011.
The ‘Trapeze’ study, an academic clinical trial for patients who have Prostate Cancer which has spread to include the bone (metastatic prostate cancer), was coordinated by The CRCTU with Professor Nick James the Chief Investigator and is now closed to recruitment.
This trial compared different combinations of treatment in patients whose prostate cancer that had spread to the bones and had not responded to hormone therapy, to determine whether or not the upfront use of bone targeting agents with chemotherapy improves clinical outcomes.757 patients took part. The trial started out as a ‘Phase II’ study, investigating the effectiveness of giving docetaxel together with prednisolone, with or without zoledronic acid and/or radioactive strontium and the side effects.This was then expanded into a phase III trial with a larger number of patients. This is a novel approach, as normally differing phase trials are separate.
The results, presented at the American Society of Clinical Oncology meeting in 2013 showed that radiotherapy with injectable strontium given after chemotherapy with docetaxel, increased the length of time until the disease progressed. In addition, it was shown that zoledronic acid significantly reduced the average time until the occurrence of ‘skeletal-related events’ caused by bone metastases. These ‘events’ include pathological fractures, spinal cord compression, or the need for radiation or surgery to the bone. Further health economic and quality of life analyses are pending.
Another exciting prostate cancer trial that is being run by the CRCTU and has recently opened is the ‘AdUP’ trial, investigating a new gene therapy treatment that helps the body’s own immune system fight prostate cancer, in addition to targeted ‘suicide gene therapy’. The trial is aimed at prostate cancer patients whose cancer has returned after being treated with radiotherapy and is no longer responsive to hormone therapy, but remains contained within the prostate. This condition affects around 3,000 patients every year.
The treatment is in 2 parts. The first part is an injection directly into the prostate of modified adenovirus (the virus responsible for the common cold). The virus is unable to replicate in the body and can produce an enzyme called nitroreductase (NR) and an immune agent called GM-CSF. Once inside the cells, one of the genes carried by the virus causes the cells to produce GM-CSF, which activates the body’s own immune system, attracting white blood cells to attack the cancer. Two days later, patients receive an infusion of a drug, which becomes active on coming into contact with NR and starts to kill cancer cells. The aim of this trial is to investigate the safety of this combined treatment.
The modified adenovirus was developed by the Gene Therapy Group, led by Dr. Peter Searle, in the School of Cancer Sciences at Birmingham and has taken 15 years of work with support from the Medical Research Council.
There is currently no approved curative treatment for these patients. The Chief Investigator, Mr Prashant Patel is hopeful that the AdUP treatment could delay or prevent the progression to metastatic disease, offering new hope to patients with prostate cancer.
“If this works, 15 to 20 years from now, we could be using the patient’s own immune system in this way to fight early onset prostate cancer so that patients won’t need painful treatments or even surgery” his colleague Mr Richard Viney said.
Last year when the first patient underwent treatment, the trial made headlines: Cold virus ‘treats prostate cancer’ for Birmingham patient (BBC News).
Though the focus of men’s health week this year is relating to health at work and stress, there are other men’s health and cancer awareness initiatives running throughout the year. Movember is well supported at The CRCTU and from the above video Mr Prashant Patel can be seen supporting the initiative with his Mo proudly!
We hope you found this insight interesting. Coming up in tomorrow’s post, a piece on an exciting and pioneering new project known as the National Lung Matrix trial for patients with advanced lung cancer.
To find out more about what goes on at The CRCTU you can follow our twitter feed here.
Further useful links:
- Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).