Cancer

Mae'r cynnwys hwn ar gael yn Saesneg yn unig.

Cancer Research UK Event

We have a wide variety of international trials in progress with experience in both solid and blood cancers.

Research areas

  • Screening and early diagnosis
  • Improved diagnosis, stratification, prevention and treatment strategies
  • Understanding the mechanisms that cause solid and blood cancers

Case studies

blood cells

Cardiff University scientists in the Centre for Trials Research are part of a UK team to develop a simple blood test capable of detecting levels of leukaemia cells remaining after intensive chemotherapy.

Background

Working alongside experts from King’s College London, a team led by Professor Robert Hills from the Haematology Clinical Trials Unit based in the Centre for Trials Research, provided crucial data from current patients with leukaemia.

The test helps predict which patients with acute myeloid leukaemia (AML) are at risk of their cancer returning in the future, helping to guide doctors on what further treatment is needed.

Professor Robert Hills, who coordinated the clinical trial and collected data for the project, said:

“The data we’ve collected from patients has given us a new insight into Acute Myeloid Leukaemia (AML).

“Looking at the disease while people are receiving treatment has given us a unique opportunity to learn much more about how best to treat.

“What we have been able to identify is a group of patients who otherwise would be thought to do quite well, who in fact have a very poor prognosis, and who are not well served currently.

“This opens up the exciting prospect that we can do the same for other groups of patients as well.”

Minimal residual disease (MRD) testing better predicts relapse

AML is diagnosed in around 2,400 people each year in the UK. Although survival rates are extremely poor overall, outlook for younger patients able to tolerate intensive treatment is better, with over half of patients under 40 years old surviving for at least five years.

Looking at the disease while people are receiving treatment has given us a unique opportunity to learn much more about how best to treat.

Dr Robert Hills, Haematology Clinical Trials Unit, Cardiff University

In research published online in the New England Journal of Medicine, scientists used a ‘minimal residual disease’ (MRD) test to predict relapse, using blood samples from 346 AML patients who had undergone two cycles of chemotherapy.

The patients all had AML driven by faults in the NPM1 gene – which is the most common genetic sub-type of the disease and accounts for a third of all cases.

The best chance of a cure involves chemotherapy and, in the case of high-risk patients, a stem cell transplant. While intensive treatment is normally successful in sending the cancer into remission, relapse is very common.

Patients usually only undergo a stem cell transplant after chemotherapy if they are adjudged to be at high-risk of relapse and are fit enough.

The researchers found that MRD testing was far superior at predicting relapse compared to current methods, which mainly rely on analysis of genetic abnormalities within individual patients’ cancer cells that influence whether they are ‘high risk’ or ‘low risk’ at the start of treatment.

International trial

The study was conducted within the National Cancer Research Institute (NCRI) AML17 clinical trial, which treated patients from across the UK, Denmark and New Zealand. All samples analysed using MRD testing were from patients determined to be at ‘standard risk’ of relapse using existing testing.

Molecular remission

The MRD test can determine if a patient is in ‘molecular remission’, which means there are no signs of the faulty molecules indicative of leukaemia cells in their blood. This can be measured to a sensitivity of one leukaemia cell in 10,000 healthy blood cells.

In 82% of cases in which the MRD test detected the presence of the NPM1 cancer gene in a blood sample after treatment, the patient had relapsed within three years. Just 30% of patients who had no detectable leukaemia cells in their blood at this stage went on to relapse within that time.

Research impact

Alasdair Rankin, Director of Research at Bloodwise, who funded the research, said:

“Treatment for acute myeloid leukaemia is highly toxic and survival rates are desperately poor, particularly for older patients.

“Preemptive treatment to prevent relapse in those most at risk would reduce the levels of toxic treatment needed and improve its chances of success.”

The findings were published online in the New England Journal of Medicine under the title ‘Assessment of Minimal Residual Disease in Standard-Risk AML’.

Funders: Bloodwise and the National Institute for Health Research (NIHR)

Chief Investigator: Professor Alan Burnett

Female researcher looking into microscope

A randomised placebo controlled trial in postmenopausal women with advanced breast cancer previously treated with a third generation aromatase inhibitor.

Background

In 2010, 49,564 UK women were diagnosed with invasive breast cancer and 11,556 died. Endocrine (hormone) therapy will cure 30% of women with undetected micro-metastatic disease but 70% will relapse and subsequently die from Estrogen Receptor Positive (ER+) endocrine resistant metastatic breast cancer.

FAKTION will investigate whether we can reverse resistance to hormone therapy by adding an additional oral drug called AZD5363.

AZD5363 is a targeted therapy that blocks the action of Akt, a cellular protein shown to cause resistance to hormone therapy. AZD5363 will be combined with fulvestrant - another hormone therapy sometimes used alone in patients who have developed resistance to Aromatase Inhibitors or tamoxifen.

Study design

FAKTION has four stages:

  • initial Phase 1b dose escalation study (stage 1)
  • subsequent Phase 2 double blind randomised controlled trial (RCT) (stages 2-4).

Phase 2 is divided into three stages as pre-clinical data support the concept that AZD5363 may be more active in tumours with PI3K/Akt/PTEN pathway activation.

Recruitment

The target recruitment for FAKTION is 150 patients.

Working alongside study sites with similar eligibility criteria

Phase 1b (now closed) reached its target of nine patients. Recruitment for Phase 2 has been slower than anticipated. Competing AZ-funded studies FURVA and MANTA recruit the same patient population restricting sites available to open FAKTION.

We are collaborating with the MANTA study to recruit their top accruing sites when their recruitment ends (August 2016). We believe by attracting these sites to a trial with almost identical eligibility criteria we will facilitate better patient accrual to FAKTION than pursuing sites with relatively little research activity that have not already expressed interest to open MANTA, FAKTION or FURVA.

Research impact

This research will contribute significantly to international knowledge base and could lead to significant change in clinical practice.

News reports including Chief Investigator and participating patient views on this study in ITV Wales news, Wales Online and the Experimental Cancer Medicine Centre (ECMC) Network.

Funders: AstraZeneca and Cancer Research UK

Large group of people looking up at camera

A study to assess whether the addition of an antibody can prevent regrowth of cancer cells in the oesophagus and thereby improve survival.

Background

Oesophageal cancer patients are often treated with chemo-radiotherapy as an alternative to surgery. Although this is an effective method for disease control, patients typically have loco-regional recurrence (disease within the area previously radiated by radiotherapy). This is partially due to radiotherapy resistant cells.

The SCOPE1 trial aimed to assess whether the addition of an antibody called cetuximab, which targets a protein responsible for cell growth on the outside of the cell, may prevent regrowth of cancer cells within the radiated area and ultimately improve overall survival.

Study design

SCOPE1 was a randomised phase II/III multicentre clinical trial.

All patients were randomised to receive chemo-radiotherapy with or without cetuximab. Sites were asked to follow a detailed radiotherapy protocol when outlining and planning radiotherapy for SCOPE1 patients. A pre-trial test case was completed by each investigator prior to site activation as a quality assurance measure to ensure standardisation of treatment across the trial.

Involving the public and patients

A patient representative was involved in the design and management of the trial and they attended the regular trial management group meetings. In addition, members of the public were involved in the review of the trial during the funding application process with Cancer Research UK.

Research impact

The Phase II analysis of the data showed that the addition of cetuximab was less favourable to chemoradiotherapy alone in terms of overall survival and toxicity. This outcome was consistent with other randomised trials conducted at the same time comparing similar types of antibody therapies with standard therapy at other tumour sites.

Although the addition of cetuximab was not recommended, the overall survival in the chemo-radiotherapy arm without cetuximab was higher than previously reported in UK and US studies and even surpassed the rate predicted within the cetuximab arm at the start of the study.

Furthermore, although quality of life scores dropped immediately after treatment, they recovered more quickly than has been found with surgery and, unlike with surgery, there is little lasting deficit.

The successful outcome of this trial was thought to be due to the detailed radiotherapy protocol, the mandated pre-trial radiotherapy quality assurance process and the positive dialogue between the Radiotherapy Trials Quality Assurance (RTTQA) team and the sites.

Study follow up: SCOPE2

Despite the improved patient outcomes seen in SCOPE1 trial, improvement in local-disease control is still needed to prevent patient relapse. To address this, we have developed the SCOPE2 trial which aims to assess whether increasing the dose of radiotherapy within the context of a high-quality RTTQA programme improves overall survival. Additionally, the trial aims to see if survival can be improved by using an early PET scan to change the chemotherapy if it does not appear to be working.

The SCOPE2 radiotherapy protocol has improved upon the SCOPE1 protocol and even more rigorous RTTQA process has been adopted from the NeoSCOPE trial. SCOPE2 also aims to champion the use of the new state-of-the-art radiation delivery system IMRT (intensity modulated radiation therapy) for treating oesophageal cancers at hospitals across the UK.

The SCOPE2 trial is now approved by ethics, the Medicines and Healthcare products Regulatory Agency (MHRA) and global R&D, and can be found on clinicaltrials.gov.

Funder: Cancer Research UK

Theme leads

Richard Adams

Dr Richard Adams

Clinical Reader

Email:
adamsra3@caerdydd.ac.uk

Yr Athro Robert Hills

Lead for Clinical Cancer Research Methodology and Portfolio Lead for Haematological Oncology

Email:
hillsrk@caerdydd.ac.uk
Telephone:
+44 (0)29 2074 4647

Dr Tracie-Ann Madden

Senior Trial Manager in Solid Tumours

Email:
maddenta1@caerdydd.ac.uk
Telephone:
+44 (0)29 2068 7953

Dr Lisette Nixon

Research Fellow - Senior Trial Manager in Solid Tumours

Email:
nixonls@caerdydd.ac.uk
Telephone:
+44 (0)29 2068 7458
John Staffurth

Dr John Staffurth

Reader

Email:
staffurthjn@caerdydd.ac.uk
Telephone:
+44 (0)29 2031 6964

Ian Thomas

Senior Trial Manager in Blood Cancer

Email:
thomasif@caerdydd.ac.uk
Telephone:
+44 (0)29 2074 5397

Cardiff University collaborators

Oliver Ottmann

Yr Athro Oliver Ottmann

Professor and Head of Haematology

Email:
ottmanno@caerdydd.ac.uk
Telephone:
+44 (0)29 2074 2375

Funding

The Wales Cancer Trials Unit based in the Centre for Trials Research is funded by Cancer Research UK.