International Clinical Trials Day: An inside look at clinical trials at the ICR

Image: Dispensing medicines for a clinical trial (Jan Chlebik for the ICR, 2014)

On 20 May in 1747, James Lind launched the first randomised clinical trial assessing whether citrus fruit was beneficial to sailors to treat scurvy.

More than 270 years later, clinical trials have become a crucial step in introducing innovative new treatments into patient care.

The ICR conducts a wide range of innovative clinical trials, from first-in-human studies to large multicentre randomised comparative trials.

These trials are often practice-changing, assessing the latest promising treatments, often within the setting of precision medicine, to progress research from bench to bedside – ensuring the vital research carried out at the ICR and elsewhere reaches the patients who could benefit from it.

Who conducts them?

The ICR has two state-of-the-art clinical trials units, with expertise spanning the whole clinical trial lifecycle.

The Drug Development Unit (DDU) is a joint enterprise between the ICR and The Royal Marsden. The centre tests treatments for the first time in humans – called phase I trials – with the aim to explore treatments which target the molecular makeup of each individual patient’s tumours.

The ICR’s Clinical Trials and Statistics Unit (CTSU) leads on the design, conduct and analysis of phase II and III national and international cancer clinical trials looking at the effectiveness of a wide range of cancer treatments – including innovative new targeted drugs, liquid biopsies, immunotherapies and precision radiotherapy.

The ICR Clinical Trials and Statistics Unit (ICR-CTSU) leads the design, conduct and analysis of phase II and III national and international cancer clinical trials. Our findings directly influence clinical practice within the NHS and worldwide.

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Who are they for?

Over 300 patients a year now enter phase I trials in the DDU, representing the early stage of testing the effect of new preclinical drug discoveries on a variety of different cancer types.

As part of the DDU, the ICR and our partner hospital The Royal Marsden have a joint unit, the Oak Foundation Drug Development Centre, which is specifically designed for phase I clinical trials that involve patients who have a late stage cancer and have run out of treatment options.

The ICR-CTSU is one of 15 clinical trial units recognised by the National Cancer Research Institute (NCRI) for professional specialism in the development and delivery of cancer trials, directly influencing routine clinical practice within the NHS and worldwide.

It mainly focuses on breast, urological, head and neck and lung cancers, but also look at rarer cancer types including melanoma, sarcoma and ovarian cancer.

The phase II and III trials tend to involve a larger number of patients, examining the effectiveness and safety of a treatment in comparison with current standard of care.

For patients to take part in any of these trials, their current oncologist will refer them onto a particular trial that fits with their cancer type and other factors, such as age or previous treatments.

What kind of trials are on offer?

The ICR-CTSU currently have over 60 clinical trials at various stages in the clinical trial lifecycle. Here are some examples of just a few:

• plasmaMATCH – matching breast cancer patient’s genetic mutations to their treatments

This innovative multicentre phase II clinical trial – funded by Cancer Research UK, with additional support from AstraZeneca and Puma Biotechnology – will look at whether a blood test to look at tumour DNA found in the bloodstream can be used as an alternative to the invasive biopsies currently used to identify the genetic mutations present in breast cancer.

Certain genetic mutations can make patients more susceptible to a particular cancer drug. Based on the results of the blood test, the patients will be split into different targeted treatment groups. Researchers will then explore whether certain groups of these patients may benefit from a treatment targeting their type of cancer.

• CHHiP – reducing the number of radiotherapy trips for prostate cancer patients

With a total of 3,216 participants and funded by Cancer Research UK, the CHHiP trial looked at whether giving a larger but fewer doses of radiotherapy (meaning fewer appointments) could improve the therapeutic effect of the treatment for prostate cancer patients, shrinking the tumour or reducing damage to the healthy surrounding tissue.

The five-year outcomes found that this method, called hypofractionated radiotherapy, was able to slow prostate cancer progression, and could save each patient 17 hospital visits for radiotherapy. This was therefore recommended as a new standard of care for prostate cancer.

Following on from CHHiP, the PACE trial is looking at the same approach of hypofractionated radiotherapy, but this time using stereotactic body radiation therapy, a method which gives radiotherapy from many different angles around the body to allow a higher dose of radiation to be targeted precisely to the tumour, reducing the effects on surrounding tissue. 

PACE will see if radiotherapy for localised prostate study can be given in just 5 doses.

• CASPS – a new drug for a rare soft tissue cancer

This international phase II trial examined the ability of the drug cediranib to halt disease progression in patients with alveolar soft part sarcoma, a rare slow-growing soft tissue tumour. This disease normally affects the different types of soft tissue, such as muscle, fat or nerves, in the leg.

The trial recruited 36 patients from 12 sites in the UK, Australia and Spain, following the effects of cediranib on these cancer patients over five years.

• TOPARP – using an ovarian drug for prostate cancers with the same defects 

The TOPARP trials are separated into two parts, A and B – both of which looked into the use of olaparib in prostate cancer patients who have run out of treatment options.

Olaparib was developed at the ICR and is licensed for treatment of women with ovarian cancer and inherited BRCA mutations. It works by inhibiting the protein PARP, preventing its normal function of repairing cancer cells, resulting in targeted killing of the cancer cells.

TOPARP-A found that men with prostate cancer which has defects in the genes responsible for DNA repair benefit from treatment with olaparib – stopping prostate cancer growth and reducing prostate specific antigen (PSA) levels, which are used as an indicator of prostate cancer risk.

TOPARP-B looked further at the anti-tumour effects of olaparib in men with DNA repair-deficient prostate cancer, assessing its safety and how long patients remain alive and free from disease.

• PIVOTALboost – giving prostate cancer treatment a boost of radiotherapy

This Cancer Research UK-funded study is currently recruiting men who have been diagnosed with prostate cancer that has a relatively high risk of it coming back.

It is examining whether having radiotherapy to the lymph nodes in the pelvis as well as the prostate, and whether giving a “boost” of radiotherapy to a targeted area of the prostate improves outcomes for patients compared to standard prostate radiotherapy.

What impact do our trials have?

The standard of care for many cancers has already been improved through the findings of ICR clinical trials, improving the outcome for patients by personalising treatments and reducing side effects.

The ICR continues to conduct trials to push progress, ensuring patients feel the impact of the world-class research and benefit from it. The ICR-CTSU also ensures it shares its clinical trial data and samples responsibly with the wider research community in an effort to improve science and medical knowledge about cancer.

The Director of the ICR-CTSU, Professor Judith Bliss said:

“Clinical trials are a crucial part of therapeutic development, whether testing promising new treatments against the current standard of care or discovering new ways to intervene to treat the disease. They have a hugely important role in ensuring the safety of new drugs and reducing the amount of side effects patients experience during their treatment.

“We’re extremely grateful to everyone who takes part in clinical trials, who by doing so are helping others, future patients, access the best new treatments.

“We’d really like to see more patients in the UK, who might be eligible to take part in a clinical trial, offered the opportunity to do so by their oncologists. Although new drugs don’t work for everyone, they can offer hope and options for patients who have run out of alternatives.”

To find out more about how to get involved in clinical trials, please visit our patients and public page, or find a list of all ICR clinical trials on our clinical trials page.