Archive for ‘cancer’

June, 2014

Clinical Trials in Skin Cancer at the CRCTU

Dr Joshua Savage (@joshsavage)

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About 115,000 people are diagnosed with skin cancer every year in the UK. The majority of these cases are the non-melanoma types of disease, such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), although there are rarer sub-types of the disease. Despite being very common, non-melanomas are less life threatening and are often successfully treated if caught early, which is more achievable compared to other cancers due to the visibility and palpable nature of skin cancer.

Around 13,000 patients have the more serious, and often more aggressive, malignant melanoma which results in over 2000 deaths per year. In the last 30 years, the rate of malignant melanoma has risen faster than any of the other 10 most common cancers, and its incidence is disproportionately higher in younger people compared to other cancers, with a 1/3 of cases being in people under 55. As with all cancers, there are many risk factors involved in the development of the disease but sun exposure is thought to be the main cause, with most lesions occurring on sun exposed areas of skin. Genetics, namely skin colour, and a history of sunburn and the use of sunbeds also increase the risk of the disease.

There have been great improvements in the treatment of malignant melanoma in the last 30 years, with 5 year survival now at 84% for men and 92% for women. These patients are usually treated with surgery then a combination of radiotherapy and chemotherapy. Earlier this month, very promising results were presented at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago and widely covered in the media, for a “ground-breaking” new immunotherapy by pharmaceutical company Merck, called MK-3475, or more commonly known as pembrolizumab. This drug works by targeting PD-1, or Programmed Death receptor, a protein used by cancer cells to avoid detection by the immune system. This is one of several drugs in a new class of treatments called ‘immune checkpoint blockers’, that ‘modulate’ the immune system allowing the body’s own defences to combat the disease in a more targeted manner than conventional chemotherapy that non-discriminately kills rapidly dividing cells. Currently, 1 year survival for advanced melanoma is 10% for men and 35% for women; encouragingly, 70% of patients on pembrolizumab were still alive after 1 year. These exciting developments are welcome news that will hopefully result in new treatments and a change in standard care for this group of patients who previously had a very poor prognosis.

At the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham, we have a growing portfolio of skin cancer trials. UKMCC-01, is a phase II study using pazopanib to treat patients with metastatic merkel cell carcinoma (MCC), a very rare (400 patients per year in UK) and aggressive form of non-melanoma cancer with a poor prognosis after first line treatment. Pazopanib is currently licensed in the UK to treat advanced renal cell carcinoma and works by targeting platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, amongst other targets, both which have been shown to be mutated or over-expressed in MCC tumours.

We will also soon be opening another phase II trial called SPOT; Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments. SPOT aims to prevent the development of cutaneous SCC from actinic keratoses, asymptomatic red scaly lesions on sun exposed areas of the skin, which are generally regarded as precursors to cSCC. This feasibility study will examine how patients cope with two different topical treatments, 5-fluorouracil and imiquimod versus standard care (sunscreen). SPOT will observe this in a sub-set of patients who have received organ transplants and are taking immunosuppressive medication to prevent organ rejection. These patients have previously been shown to have a much higher incidence of cSCC and other cancers, which once again demonstrates the vital role that the immune system plays in combatting cancer.

Researchers at the CRCTU are working with colleagues across the science and research community to maximise on developments and ensure they reach patients rapidly and change the course of this devastating disease. Novel treatments along with early diagnosis and prevention are key to changing the course of this cancer, Justine a survivor of skin cancer reminds us why we must continue with this plight.

Dr Joshua Savage is a Trial Coordinator at Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham. Follow Dr Savage on Twitter @joshsavage

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June, 2014

How the CRCTU is addressing overtreatment of ductal carcinoma in situ (DCIS)

Miss Claire Gaunt

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The NHS Breast Screening Programme was established in the late 1980’s with the aim of detecting invasive disease at an early stage and reducing deaths from breast cancer. This has been achieved but, an incidental consequence has been the increasingly common finding of DCIS, a diagnosis almost unheard of before mammographic imaging. Historically, DCIS was thought of as a form of early breast cancer that would become an invasive breast cancer if left untreated.

DCIS describes abnormal cells in the milk ducts of the breast. It is divided into 3 types; low, intermediate and high grade. Low grade DCIS looks similar to normal breast cells and high grade DCIS looks similar to cancer cells. When diagnosed, all DCIS is currently removed by surgery because of concern that it may progress to an invasive cancer. If DCIS is indeed an early form of breast cancer, then removing it would have lead to a decrease in the incidence of invasive breast cancer. This has not been the case but, surgical treatment of DCIS, often mastectomy, has remained unchanged since the 1950’s, despite evidence that removing DCIS does not prevent invasive cancers. DCIS is almost always diagnosed as a result of calcification found on mammograms and accounts for 20% of all breast ‘cancers.’ Evidence shows that many women are being treated for a condition that will never become a clinical problem if left undiagnosed. This is known as ‘overdiagnosis’ and ‘overtreatment’. Experts agree that not all untreated DCIS will become breast cancer.

An independent review of the UK National Health Service Breast Screening Programme reported on the benefits and harms of breast screening. This concluded that breast screening saves lives but acknowledged the existence of overtreatment. Consequently, randomised trials were recommended to elucidate the appropriate treatment of screen-detected DCIS and to gain a better understanding of its natural history. The aim of overtreatment trials is to stop treating women who do not need treatment and to better treat those who do.

The Low Risk DCIS Trial (LORIS) is a large phase 3 trial designed to address the recognised issue of overtreatment of low risk DCIS. This trial is not for patients with high grade (the most common) DCIS.

The study is being run by the Cancer Research UK Clinical Trials Unit (CRCTU) which has a long history of running successful breast cancer treatment trials and is an integral part of the Birmingham Surgical Trials Consortium (BiSTC) at the University of Birmingham. The trial is led by Miss Adele Francis, Consultant Surgeon at the University Hospitals Birmingham NHS Foundation Trust. The trial will recruit almost a 1000 women with low risk DCIS, who will be randomised to the current standard treatment which is surgery or to omit surgery and have active monitoring with annual mammograms. The LORIS trial, through it’s clinical and translational research will establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (both psychological and physical) and whether those patients who do require surgery can be identified by pathological and radiological means. When this trial is reported, patients and clinicians will be able to make an informed choice about treatment options.

University Hospitals Birmingham NHS Foundation Trust will be the first centre to begin recruit patients in to this ground-breaking trial. In the coming months, you can follow our progress on twitter at @CRCTU

Miss Claire Gaunt is a Team Leader in the Cancer Research UK Clinical Trials Unit at the University of Birmingham.

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June, 2014

Quality Management at the Cancer Research Clinical Trials Unit (CRCTU)

Isobel Hawley – Quality Assurance Manager

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When I was a child my father drummed into me the importance of paying attention to detail. His actual words were, “always pay absolute attention to absolute detail”. I remember a lot of rolling of eyes (on my part), but he was right (and still is for that matter – thanks Dad!). Now it’s my job to pay attention to detail – as Quality Assurance Manager at the Cancer Research UK Clinical Trials Unit (CRCTU). It certainly wasn’t what I was planning when I graduated with a degree in Russian and French…but many years later, my focus in life changed when a friend’s 3 year old child died of cancer. My previous mild interest in things medical (a lifelong addiction to watching Casualty on Saturday nights) developed into an earnest desire to make a contribution to cancer research, and in 2006 I applied for a job as a Clinical Trial Monitor at CRCTU in the University of Birmingham and I’ve been a member of the Quality Management Team ever since.

Clinical Trials are vital for improving cancer treatments and making them available to patients. The Quality Management Team plays an important role in supporting the conduct of clinical trials at CRCTU, by developing and maintaining a Quality Management System which provides a framework of Standard Operating Procedures, tools and templates to assist all staff in conducting trials to the highest possible standards and ensures adherence to relevant legislation. In the UK, the conduct of clinical trials of Investigational Medicinal Products (trial drugs) is governed by complex legislation and guidance including the 2004 Medicines for Human Use (Clinical Trials) regulations, the Data Protection Act, the Research Governance Framework, Good Clinical Practice and the Declaration of Helsinki.

The regulator in the UK is the MHRA (Medicines and Healthcare Products Regulatory Agency) and CRCTU is subject to inspection at regular intervals. The legislation has recently undergone a review and will soon be replaced by a new European Clinical Trials Regulation which aims to speed up and streamline the conduct of trials across Europe. It is hoped that the new Regulation will achieve its aims – many of the paediatric trials coordinated by CRCTU need to embrace international collaboration in order to recruit sufficient patients to complete the trial in an appropriate timeframe; recently the BEACON trial for children with neuroblastoma opened to recruitment in France and will open in further European countries over the coming months.

Our team of dedicated Monitors travel the length and breadth of the UK, visiting the hospitals where the clinical trials take place. The team is currently responsible for on-site monitoring of more than 30 trials, across multiple diseases (breast cancer, prostate cancer, lung cancer, leukaemia, sarcoma and all paediatric cancers) including the AdUP prostate cancer trial mentioned in Monday’s blog and the STOMP trial for lung cancer patients discussed in Tuesday’s blog. The Monitors meet with the Clinicians and Research Nurses to discuss the trial, providing training, updates and feedback from the Trials Office and a friendly face to help out with any queries. They perform checks on the paperwork at the hospital site – reviewing the medical notes of the trial patients to ensure that all patients are eligible for the trial according to the protocol criteria, checking that the patients have given their written consent to participate in the trial, that the correct trial treatment protocol has been followed and any adverse effects of the treatment have been reported to CRCTU. These on-site monitoring visits help to safeguard the rights and well-being of the trial patients and ensure high-quality data is obtained for analysis by the trial statisticians, ultimately leading to evidence-based improved treatments for patients with cancer.

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June, 2014

Early Phase Clinical Trials in Lung Cancer at the CRCTU

Dr Laura Crack

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Lung cancer is a devastating and very common healthcare problem. Lung cancer is the biggest cause of cancer death in the UK, accounting for more than one in five cancer deaths and is the second most common cancer in both men and women. Recent campaigns such as the plain packaging campaign aim to reduce the numbers of people smoking, particularly targeting children and young adults. Whilst these campaigns targeting environmental and lifestyle factors are crucial to reducing incidence of lung cancer, new and more effective treatments are urgently needed to increase the chances of surviving this devastating disease.

The Cancer Research UK Clinical Trials Unit (CRCTU) has designed and run many clinical trials for both main types of lung cancer (small cell and non-small cell lung cancer) patients over the past 2 decades. A good example of this is in small cell lung cancer (SCLS), the STOMP Trial, which is investigating the safety and activity of a drug (Olaparib) which prevents cancer cells from repairing damage to their DNA; by inhibiting a molecule called PARP. This trial, led by Professor Penella Woll, is actively recruiting patients around the country. The STOMP trial is due to run for another year and will be asking if Olaparib can be used as maintenance therapy for people with SCLC, whether it can increase the length of time people live with the disease and can it be used as maintenance therapy for SCLC.

Because of this expertise, the CRCTU and the University of Birmingham’s Gary Middleton, Professor of Medical Oncology, have been selected to lead on the National Lung Matrix trial; a joint initiative between the University of Birmingham, Cancer Research UK with pharmaceutical partners AstraZeneca and Pfizer. This trial will utilise an existing network of Experimental Cancer Medicine Centres (ECMCs) across the UK to deliver a plethora of drugs to lung cancer patients. Patients will be stratified according to genetic abnormalities in their cancer. This information will be generated in phase 2 of Cancer Research UK’s Stratified Medicine Programme, which was launched in April this year. The trial is due to open to recruitment later in 2014. Once open the National Lung Matrix trial will see cancer treatment moving towards the promise of personalised medicine where a patient’s treatment is guided by the individual genetic make-up of their cancer.

This advancement has been made possible through the Cancer Research UK Stratified Medicine Programme which has looked to establish a network for nationwide molecular testing that will form a vital platform to launch future targeted treatments. Colleagues in Birmingham have been acting as a technology hub for the stratified medicine programme and are in an excellent position to help inform this new stage of cutting edge early phase clinical trials.

TraxerX is another exciting example of the rapidly developments in personalised medicine for lung cancer patients across the country. Researchers in Birmingham are working with nationwide colleagues to further their understanding of lung cancer, how it adapts and responds to treatment along with where its Achilles heels are.

A new era is dawning and Lung Cancer researchers and clinical teams are pushing boundaries to change the devastating effects of a lung cancer diagnosis. Birmingham’s CRCTU is working collaboratively with many leaders in the field to ensure that effective developments reach patients faster.

Dr Laura Crack is EDD Team Leader in the School of Cancer Sciences at the University of Birmingham.

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June, 2014

Spotlight on the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham

Mr Clive Stubbs and Dr Steve Johnson

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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.

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