Clinical trials

PreOperative PreRAdIotherapy Tumour Treating Fields (PORTRAIT) is a Phase I study that will test the safety and feasibility of Optune administered preoperatively and preradiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). Participants will be required to undergo additional MRI sequencing scans and provide blood, tear fluid and tissue samples over a maximum of 6 months. After the study patients will follow their standard treatment pathway.

Cancer of Unknown Primary (CUP) is where cancer cells are found in the body but the place the cancer began is not known. It is the 6th leading cause of cancer death in the UK and the prognosis is poor with a median survival of 6-9 months. There is a higher than average incidence of CUP in the North West (NW) of England (population of 7.4 million). Precision medicine has transformed treatment strategies in known tumour types, however in CUP there remains an urgent need to better understand CUP molecular characteristics to establish potential roles for novel therapeutic strategies. Treatment options remain limited due to difficulties in determining the primary site of the tumour and the lack of access to validated biomarkers. Access to good-quality tissue for molecular profiling remains a huge challenge in CUP. The emergence of liquid biopsies (sequence DNA in a blood test) as a source of biomarkers is also gaining rapid ground and this study aims to explore the potential utility of liquid biopsies in CUP.

The goal of this interventional study is to see if the daily use of red light therapy called photobiomodulation can help sore skin and sore mouths in children having radiotherapy. All children aged 0-16 years old who are receiving either proton or photon radiotherapy treatment, except to the brain only, will be asked if they would like to join the study. The main questions it aims to answer are: 1. Does the use of red light therapy help the skin side effects in children and young people undergoing proton or photon therapy? 2. Does the use of red light therapy help the mouth side effects in children and young people undergoing proton or photon therapy in the head and neck area? Researchers will compare the patients enrolled on to the study with a like for like historic patient to see if red light therapy improves the sore skin and sore mouths caused by proton or photon therapy. Participants will have a daily treatment with red light therapy alongside their daily proton or photon treatment fraction.

This study is a retrospective, proof-of-concept sample study to investigate a novel histological finding within the primary melanoma tumour in a large population of melanoma patients to assess its prognostic significance. This is a aims to validate the striking observation that a cross-talk between fat cells and leukocytes at the primary melanoma site promotes metastasis. In our unpublished pilot study, we have discovered an interesting finding whereby inflammatory cells extend from the tumour to and invading fat in the subcutaneous tissue and/or around the appendageal structures in the dermal skin in metastatic melanomas with distinct architectural changes within the fat. This finding was consistently present in metastatic and absent in non-metastatic melanomas. This new finding has both clinical and pathophysiological credence. Archival tissue blocks or human cell lines will be used in the first instance. As mitigation, experiments will be repeated with conditioned media obtained from co-culture of mixed primary immune cells obtained from peripheral blood mononuclear cell (PBMCs) and adipocytes induced from stem cells. This study aims to: * Investigate if the crosstalk between fat cells and tumour-infiltrating inflammatory cells defines the aggressiveness of primary cutaneous melanomas. * Identify and perform biological spatial analysis of the inflammatory cells between the tumour and fat in the primary tumours. * Investigate the interactions of fat cells and/or inflammatory cells in mediating melanoma cellular plasticity. The patients have not provided consent and will be justified in this application

In the UK 20,000 people develop urothelial bladder cancer each year with 75-80% having Non-Muscle Invasive Bladder Cancer (NMIBC). The current standard of care for patients with High Risk-NMIBC (HR-NMIBC) is either surgery to remove the tumour (transurethral resection of bladder tumour; TURBT) followed by BCG (Bacillus Calmette Guérin, an immunotherapy drug) given directly into the bladder, or surgery to remove the bladder (cystectomy). BCG is given weekly for six weeks followed by maintenance treatment up to 3 years. However, in up to 50% of patients their cancer returns (recurrence) or gets worse (progression) after BCG and 25% stop treatment due to side effects. Globally BCG supply has been restricted in recent years has increased HR-NMIBC recurrence rates and costs. Improved treatments are required, to prevent recurrence, progression and cystectomy, and mitigate the effects of unpredictable supply. Trimodality treatment (TMT) is maximal TURBT + radiotherapy + a radiosensitiser (gemcitabine, mitomycin C/fluorouracil or carbogen/nicotinamide) and is an equivalent alternative treatment to cystectomy for muscle-invasive bladder cancer (MIBC). TMT is not routinely used for HR-NMIBC. A study found that 54% of HR-NMIBC patients who received TMT did not have recurrence within 5 years. Modern radiotherapy is expected to further improve outcomes and minimise side-effects. Patients will be randomised 1:1 to BCG or radiotherapy with radiosensitisation. Patients randomised to the experimental arm will receive 55Gy in 20 fractions. Investigators can then choose from three different options for the radiosensitiser. TRAIN will test if radiotherapy with radiosensitisation improves outcomes for people with HR-NMIBC compared to BCG. TRAIN will recruit 328 patients with HR-NMIBC following maximal TURBT. All patients will be followed up for a minimum of two years to record their response to treatment.

The goal of this clinical trial is to understand whether the Magnetic Resonance Linear Accelerator (MRL) could expedite Radiotherapy treatment for Metastatic Cord Compression (MSCC) by removing the need for a planning CT (pCT) scan prior to treatment. Radiotherapy will be delivered in one appointment on the MRL and compared to the standard of care of two appointments: a CT scan and a Radiotherapy appointment. The main questions it aims to answer are: * Can the MRL deliver successful treatment of MSCC in a single 1-hour appointment? * Can the MRL treat participants within 24 hours from the doctor's decision to treat? * Did it take less time from consent to completion of treatment when patients were treated on the MRL? * Do the questionnaire scores reflect satisfaction with treatment on the MRL? Researchers will compare treatment on the MRL in one appointment to a group receiving standard of care radiotherapy in two appointments. Participants in both groups will receive the same prescription of 8Gray (Gy) in one treatment (fraction) delivered with one posterior-anterior beam as per our department policies and national standards. Participants will be asked to complete an optional questionnaire prior to treatment to monitor the diversity of the study population. This questionnaire is anonymised, no personal data that could identify a participant is collected on this questionnaire. After treatment participants will be asked to complete an experience questionnaire, to assess treatment experience. Once the questionnaire is complete active participation in the trial is no longer needed, researchers will monitor participants notes for up to 12 months after treatment to record participant well being and function.

To determine if the investigators are able to deliver highly focused, intense radiation to tumours in the abdominal region or chest cavity whilst limiting the dose to surrounding organs using a high field strength MR-Linac.

Non-patient volunteers will be scanned on the MR-Linac and MRSIM to facilitate the development, optimisation and validation of MRI protocols at The Christie NHS Foundation Trust.

Proton Beam Therapy (PBT) and Evaluative Commissioning in Protons (ECIP): PBT is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the United Kingdom, in Manchester and London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT. ECIP is a programme of studies exploring the role of PBT in different types of cancer funded by NHS England. ECIP studies are not randomised, eligible patients will be offered PBT. Any eligible UK patient can be referred, and accommodation is available for patients who don't live close to a PBT centre. The main benefit of PBT, compared with standard photon radiotherapy, is predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects. SUPERMAN: SUPERMAN is a study within the ECIP programme. It is sometimes not entirely clear whether PBT or photon radiotherapy is better for the treatment of a patient with abdominal neuroblastoma. The aim of SUPERMAN is to choose the best radiotherapy technique and to better understand how to monitor and adapt PBT for these patients.

This project aims to characterise the tumour cell and tumour microenvironment of colorectal cancer peritoneal metastases, understand molecular changes leading to colorectal peritoneal metastasis, identify potential biomarkers and novel treatment strategies.

Patients ≥ 18 years old who have been diagnosed with appendiceal cancer with peritoneal metastases, have had cytoreductive surgery, have availability of archival tumour tissue and have consented to our institutional biobank program or have a waiver of consent for deceased patients who have not had the opportunity to provide biobank consent (requested at the time of ethics review). Descriptive analysis of the proportion of genetic mutations identified in appendiceal cancers. This is given by the percentage of pathogenic mutations in the peritoneal metastasis compared to the primary tumour.

In the UK over 22,000 people undergo pelvic radiotherapy treatment per year, for several types of cancers including prostate cancer. The investigators want to investigate whether there are any differences in the bacteria in the bowel in patients with prostate cancer and whether these change during treatment. The aim of this study is to analyse the bacteria from the stool of patients undergoing radiotherapy for prostate cancer. The investigators will also look for any changes in the urine, blood and using rectal swabs that might be a surrogate for what is happening in the gut at the same time. They will collect food frequency/ food diary information for each patient alongside health questionnaires. The investigators aim to recruit approximately 50 patients diagnosed with prostate cancer due to undergo radiotherapy over a two year period. Patients will be recruited across 2 sites (Rosemere Cancer Centre, Lancashire Teaching Hospitals Trust and The Christie NHS Foundation Trust).

Yttrium-90, attached to microspheres, usually referred to as 90Y-microspheres or Y-90 radioembolisation, can be used in some cases to treat patients with liver tumours or liver metastasis. The treatment aim is to infuse the 90Ymicrospheres into the patient's liver. The microspheres get trapped in the lesions of micro-blood vessels while the yttrium-90, a radioactive compound, delivers radiation doses locally at these sites and damages the diseased cells. Therapy is performed in such a way the 90Y-microspheres are localised in the tumour areas minimising damage to the healthy liver tissue. This treatment requires many steps involving professionals from different medical disciplines. Patients are scanned in the nuclear Medicine Department on a gamma camera the day after the treatment. This scan is referred as Y-90 bremsstrahlung-SPECT. This posttherapy scan provides a 3-dimensional (3D) image of the distribution of the therapeutic agent in the patient's abdomen so an assessment of how much of the therapeutic agent has gone to the sites of disease can be performed. In this research project, the investigators would like to evaluate an alternative post-therapy scan to the one routinely performed on the gamma camera. The alternative scan is done on a PET-CT scanner and is referred to as Y90-PET-CT. This type of scan has been reported to provide improved quality images, providing more accurate information on the distribution of the patients therapeutic dose. For this research project, the investigators will invite a small number of patients undergoing this therapy to be scanned twice after treatment: with the current post-therapy scan on a gamma camera; and with the newly proposed scan method, Y90-PET-CT. Depending on the outcomes of this project, assessed by an expert panel of radiologists and medical physicists, the investigators will determine whether we will introduce this new scanning method into clinical practice in the future.

Proton Beam Therapy (PBT) is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the UK, one in Manchester and one in London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT treatment. Evaluative Commissioning in Protons (ECIP) is a programme of studies that explore the role of PBT for patients with different types of cancer. They are funded by NHS England. ECIP studies are not randomised studies, which means that all eligible patients will be offered proton therapy. Any patient in the United Kingdom (UK) can be referred, and for patients that need to travel far to their nearest centre, accommodation will be available. The main benefit of PBT, compared with photon radiotherapy, is the predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects. PRONTO is a study within the ECIP programme exploring whether PBT can reduce treatment side effects for patients with salivary gland cancers who need radiotherapy following surgery. Whilst radiotherapy is associated with good cancer control, it commonly causes problematic side-effects such as loss of taste and dry mouth. These can be permanent and can negatively affect someone's quality of life. PRONTO's main aim is to see if PBT can reduce the loss of taste following radiotherapy. Participants in PRONTO will be closely monitored by the medical team and with questionnaires. The patient experience will be compared to what we would expect with standard photon radiotherapy.

Proton Beam Therapy (PBT) is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the United Kingdom (UK), in Manchester and London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT. Evaluative Commissioning in Protons (ECIP) is a programme of studies exploring the role of PBT in different types of cancer. The studies are funded by NHS England. ECIP studies are not randomised studies, which means that all eligible patients will be offered PBT. Any eligible patient in the UK can be referred, and accommodation is available for patients who don't live close to a PBT centre. The main benefit of PBT, compared with standard photon radiotherapy, is the predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects. EMPHATIC is a study within the ECIP programme. In EMPHATIC, the investigators are looking to see whether a combination of treatments, including PBT, chemotherapy and a liver transplant, can be used to treat patients with cholangiocarcinoma (bile duct cancer). EMPHATIC offers patients whose cancer can't be removed with surgery (unresectable) a potentially curative treatment option. There is evidence that liver transplant is a curative treatment option in patients with cholangiocarcinoma. There is a risk that the cancer may grow or spread whilst waiting for a transplant, potentially making patients ineligible. PBT and chemotherapy is thought to be the best way to control the cancer, until a liver transplant can be performed. EMPHATIC will look at how a combination of PBT and chemotherapy, followed by a liver transplant, can be used to curatively treat patients with unresectable cholangiocarcinomas.

How does plasma Epstein-Barr Virus (EBV) DNA level change during definitive radiation therapy for nasopharyngeal carcinoma (NPC) in the teenage and young adult cohort and does it correlate with outcomes?

The goal of this clinical trial is to investigate adaptive therapy in late-stage cutaneous melanoma. The main question it aims to answer are: If the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour less resistant to the treatment, an increasing the time it takes for the disease to progress? Participants will * Receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first. * Attend fortnightly visits to hospital. * Complete EORTC QLQ-C30 and PRO-CTCAE questionnaires, prior to treatment, every 12 weeks and at the point of cancer progression, to assess quality of life. Researchers will compare the adaptive therapy participant arm with a standard of care arm to answer the research question described above.

The primary aim of TARGET National is to establish a national framework to offer molecular profiling of circulating tumour DNA and/or tumour tissue (optional) to patients with advanced solid cancers referred to any of the Experimental Cancer Medicine Centres (ECMCs) across the UK, in order to help decision making for allocation to molecularly targeted experimental cancer treatments. Patients will be allocated treatment using a national Molecular Tumour Board to find the most suited therapies based on their molecular profiling results. This study aims to recruit up to 6,000 patients with advanced solid tumours across 5 years and proposes to collect blood samples, archival tumour tissue and fresh tissue (optional) The data may also be used for future development of predictive cancer biological markers, the design of clinical trials involving new or existing drugs, discovery of new genetic targets and exploring how resistance to specific anticancer agents arises in patients to help improve future cancer treatment management.

Recent advances in understanding how cancer develops and spreads have led to effective new treatments and improved outcomes for patients with melanoma. However, we know that these new treatments do not work for all patients: some do not respond to them and some initially respond but then develop resistance. The overall aim of this study will be to collect tumour biopsies, biomarkers present in the blood, and other biological specimens which can be used to try to understand why resistance to anti-cancer treatment occurs, and to develop predictive biomarkers of this resistance in patients with locally advanced and metastatic malignant melanoma. The study will be open to NHS patients aged 16 and over, who have been diagnosed with advanced melanoma, and who will be receiving treatment for their disease as part of their routine care. Patients will be asked to provide samples from tumour biopsies before, during and after treatment. We will also ask for blood samples to look at biomarkers in the blood and see how these correspond with tumour samples, which will further help us to understand treatment response. Biomarkers are substances in the body that can be measured and help indicate how a disease is developing. It is hoped that soon we will be able to monitor cancer by analysing a patient's blood samples, thus reducing the need for biopsies. As blood tests could be taken more frequently, signs that patients are becoming resistant to treatments could be picked up sooner. As well as monitoring biomarkers, we would also like to understand what happens to the healthy cells surrounding the tumour during treatment. This will improve our understanding of how cells adapt and respond to treatments, and may eventually lead to the discovery of new biomarkers to help predict which patients will develop resistance to certain treatments.