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Being a part of cancer drug discoveries

Last month, the biotech company Immunocore announced results from its phase 3 clinical trial investigating the efficacy of Tebentafusp (a new anti-tumour immunotherapy), in the treatment of patients with metastatic melanoma. If it is given regulatory approval, it is likely that the drug will enter wider clinical use next year. If it does, it will give those living with uveal melanoma (UM), a rare cancer, a new treatment option and would be the first new therapy to improve the overall survival of this group of patients in over 40 years. Susan was one of the first patients to receive the drug when it was in its early stages of development.

Susan’s Clinical Trial Experience

In 2008, what appeared to be a small spot on the top of my head turned out to be melanoma. After surgery at the John Radcliffe Hospital in Oxford to remove the tumour there was no sign of recurrence, until 2012 when the melanoma had apparently spread to my lungs. It was at then that I was invited to enrol on a clinical study at Oxford’s Early Phase Clinical Trials Unit (EPCTU).

I met Professor Middleton, head of the trials unit, in 2012 following the appearance of cancer metastases in my lungs when he informed me of a new clinical trial he was leading,  investigating a drug called IMCgp100, now known as Tebentafusp. At the time, there was no way to know if the drug would help in any way. Early-stage clinical trials for a new drug are not tried and tested, the side effects are not always clear and the outcomes not always sure.

For me, in the first 30 days of the trial I experienced rashes, headaches and lethargy. Common for many undergoing cancer treatments, but unpleasant none-the-less. Throughout the whole time I was on the trial the doctors and nurses were completely honest with me.  There were no promises.  They were on a learning curve themselves and if they didn’t know the answer to a question, they said so.

However, gradually these side effects subsided, and it became clear on my scans that the tumour had begun to shrink. Later on, it had stopped shrinking, but had not grown either. After 14 drug cycles on the trial, I attended my last scan. The tumour in my lung had shrunk to an operable size, and after another operation in 2015, the cancer was removed.

I cannot tell you how wonderful it felt when I was told that there was no sign of any tumour in the left lung and that the right one was continuing its downward trend. All of this was because of an experimental drug in an ever-evolving trial that I was part of.

At the time it didn’t occur to me that my experience was laying the ground work for the introduction of a new drug into common use.

From being told I had 18 months left to live in 2012, to being cancer free in 2015, I think my case exemplifies why clinical trials are important. It was fortunate that I qualified to be part of a first stage clinical trial in Oxford, and one that went on to help me. But even more, it is fantastic to hear that the same drug I was treated with has now gone on to complete a phase 3 trial, and have the potential to give people like me a new lease on life.

Whist clinical trial drugs are experimental until rigorously tested, the knowledge and resources of the staff at the University of Oxford is what contributed to the early identification of Tebentafusp as a potential therapy, so that it may go on to be translated into the clinic to help me and other melanoma patients.

Sometimes in life, something is so important that you have to make a decision without any knowledge of where it will lead you.

I made that decision and underwent a clinical trial that was administered under rigorously strict guidelines, with the patient’s safety as paramount

I don’t know whether the cancer will return, as I believe melanoma is a tricky devil, but I feel as if I have been given a second chance and my remission wouldn’t have been possible without the researchers and staff at Oxford involved in the development of new drugs.

About the clinical trial

Tebentafusp was tested in a phase 1 and 2 clinical trial by researchers at the University of Oxford and Immunocore, hosted at the EPCTU. The success of those trials has allowed the drug to be tested in stage 3 trials which were recently reported on by Immunocore.

The detailed results of the phase 3 trial will be submitted for publication in a peer-reviewed journal later next year. All the information about the drug will be submitted to the regulator, the MHRA, for their assessment after which it is hoped that the drug will enter the clinic.

The phase 1 and 2 trials were led by Prof Mark Middleton at the Department of Oncology.

 

Innovative drug delivery techniques show promise in clinical trials

Pancreatic cancer has a limited response to chemotherapy treatment, due to the movement of anti-cancer drugs from the blood into tumour cells being limited by cellular mechanisms such as poor perfusion, high stromal content and raised interstitial pressure. One way to overcome these challenges and increase the toxic effect of chemotherapy treatment on a tumour would be to increase drug dosage. However, this would result in the damage of healthy non-tumour cells, and would likely result in unacceptable toxicity to patients.

The aim of Professor Constantin Coussios and his team in the Institute Biomedical Engineering is to develop of drug delivery system capable of enhancing drug penetration into and around a tumour, whilst minimising toxicity to the patient. The team has so far found a successful approach, by increasing drug uptake into tumours through warming of the body, which causes vasodilation.

By using focused ultrasound (FUS) to generate heat, only defined areas (approximately the size of a grain of rice) are targeted for treatment. In combination, chemotherapy drugs such as doxorubicin can be encapsulated in a heat-sensitive lipids (ThermoDox®), so that the active drug is only released when a specific temperature is reached at a specified location, as defined by the position of the FUS beam.

Research fellows Dr Michael Gray (Dept of Engineering) and Dr Laura Spiers (Dept of Oncology) have been working with the Department of Pathology in the Oxford University Hospitals NHS Foundation Trust, to help characterise the efficacy of this approach, by assessing thermal and acoustic ultrasound properties of the ex vivo pancreas.

This new knowledge will be directly applied to patients in the new early phase clinical trial, PanDox (targeting pancreatic cancers with focused ultrasound and doxorubicin chemotherapy). This builds on the successful TarDox trial, which already demonstrated FUS-induced heating resulted in improved delivery of the ThermoDox® encapsulated chemotherapy drugs to liver metastases from various primary cancers.

The effect in the TarDox trial was such that a positive response to therapy from the tumour was seen after only a single treatment cycle in 4 out of 7 patients, even in cancers as colorectal adenocarcinoma (which is not known to respond to conventionally administered doxorubicin). These results suggest that if the cytotoxic threshold needed to successfully treat a tumour can be reached, then a positive response may be achieved without unacceptable toxic consequences on the patient.

The upcoming PanDox trial translates this approach to patients with non-resectable pancreatic adenocarcinomas. It will combine focused ultrasound to generate heat with ThermoDox® delivered into the blood.

The main aim of PanDox is to determine whether this novel approach to treating pancreatic cancer can enhance the amount of drug delivered to tumours that cannot be surgically removed. Secondary aims will assess tumour response and procedural safety. The first patients will be recruited from early 2021.

About the PanDox Team

Prof Constantin Coussios, PanDox Priniciple Investigator, is the Director of the Institute of Biomedical Engineering. His area of interest is in the study of drug delivery systems and improvement of delivery into tumours.  He founded and heads the Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL), a research group of 4 faculty and some 45 researchers working on a wide array of therapeutic applications. He is also serves as the Director of the Oxford Centre for Drug Delivery Devices.

Dr Laura Spiers is a doctor of Medical Oncology. She is currently undertaking a DPhil in Oncology with the Institute of Biomedical Engineering, investigating ultrasound-enhanced drug delivery.

Dr Michael Gray is a Senior Research Fellow, interested in the clinical therapeutic potential of ultrasound.

Funding boost for OxPLoreD early detection study

OxPLoreD is an observational cohort study sponsored by Johnson and Johnson that will recruit 1650 patients from across the UK with pre-cancerous lymphoproliferative disorders. These conditions include monoclonal B-cell lymphocytosis and monoclonal gammopathy of unknown significance that put individuals at higher risk of developing the blood cancers chronic lymphocytic leukaemia and multiple myeloma respectively.

The aim of the study is to look for new ways to find and treat blood cancer sooner by identifying clinical, genomic and immunological predictive markers of progression from these pre-cancerous conditions to malignant disease. The study will also explore the possibility of a future early intervention trial for the subgroup of patients at highest risk of progression.

OxPLoreD is one of the seven clinical trials that have received an £8m funding boost from UK Research and Innovation (UKRI) and will work in partnership with Genomics England. The funding will speed up the adoption of whole genome sequencing in the study of cancer. Genetic analysis is a critical tool that can allow clinicians to select the most appropriate treatments for each patient. In the OxPLoreD study, genetic analysis might be able to identify individuals at highest risk of disease progression that would benefit from earlier treatment. In the longer term this may also enable the identification of those people who would benefit from certain types of treatment.

Alison Cave, UKRI challenge director says:

“Research tells us that one-in-two people in the UK population will get cancer. That stark statistic shows just how important it is for us to seek new treatments. The use of genetic analysis opens new possibilities in our drive to beat cancer. The projects for which we have announced funding today are exciting pointers to future diagnosis and precision treatments”

The funding has been delivered through UKRI’s Industrial Strategy Challenge Fund’s £210m data to early diagnosis and precision medicine (DEDPM) programme. The challenge aims to combine research data and evidence from the NHS to create new and improved ways of identifying disease and treatment pathways.

Prof. Sir Mark Caulfield, Chief Scientist at Genomics England says:

“The 100,000 Genomes Project, Genomics England has analysed the genomes of over 17,000 cancer participants and this suggests that up to half have revealed mutations of potential clinical significance. The DEDPM programme is a major opportunity to expand the application of whole genome sequencing into clinical trials involving cancer where support from the ISCF is likely to deliver significant clinical benefit”

For more information about the other trials funded by this scheme, see the UK Research and Innovation announcement.

What is a clinical trial? – new video series

Discover what it means to take part in a cancer treatment clinical trial with this new video series

The Early Phase Clinical Trials Unit (EPCTU) is a specialist unit that supports the transition of cancer research findings into clinical applications for helping treat cancer.

The unit integrates oncology and haematology findings and applies them through clinical trials, with around 150 patients per year recruited into novel cancer therapies. By taking part in the clinical trials, the patients help to contribute to discovering new, more efficient or patient-focused treatments for their type of cancer in the future.

What should I expect?

When a patient is referred to EPCTU, they are often given a lot of information about what it means to be involved in the clinical trial process. This information can often be over-whelming, and in response to a patient satisfaction survey, the EPCTU created the following video series so that patients can better understand the process and how clinical trials effect their daily lives.

Video 1 – before the trial

The first video below touches on the aspects that influence a patient’s consideration in taking part in a clinical trial. Clinical trials deal with new, innovative treatments, and as such, are part of a clinical learning curve.

The video below touches on topics such as time frames and how you can expect to receive information. It’s important to give clinical trials proper consideration and understand what will happen at every stage, before reaching the later screening and eligibility process.

 

 

Video 2 – taking part

The second video is about what to expect after the screening process, once a patient has been recruited onto the trial.

Clinical trials can take a long time, both in the treatment process and the requirements later down the line after treatment. The second video in the series, seen below, outlines what to expect once you are on a trial and the benefits of seeing the trial to the very end.

 

Video 3 – trials at the EPCTU

The final video of the series, coming soon, will explain further about the EPCTU and the facilities in the centre.

It is designed for new patients to find the unit’s location and know where to find everything that they will need during the trial process.

Be sure to check back to our website homepage or this news article to see the final video in the series.

The University of Oxford announces it has dosed the first patients in a phase I study of NUC-7738