New and innovative cancer treatments go through many steps to make their way from ‘bench to bedside’. Professor Pamela Kearns, Dr Sarah Al-Jilaihawi and Dr Jessica Douglas-Pugh from the University of Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU) explain more about this process.
Globally renowned for academic excellence, the Birmingham CRCTU is responsible for the majority of academic-led children’s cancer trials in the UK and plays a crucial role in improving clinical practice and outcomes for children with cancer.
All new medicines and treatments must be thoroughly tested before they’re licensed and available for patients. Experimental medicine is hugely important in discovering and testing new, cutting-edge cancer treatments that have the potential to be more effective or cause fewer side effects and long-term health issues. When looking at children’s cancers, these ‘new’ treatments could have previously been found to be effective in adult cancers but hadn’t yet been explored in children’s cancers, or they may be entirely new treatments.
Laboratory research
Preclinical or ‘lab-based’ researchers first explore the potential of a new anti-cancer treatment through testing ‘in-vitro’ on cancer cells in a laboratory dish or test tube, or ‘in-vivo’ on living organisms. The aim of laboratory testing is to investigate whether these novel treatments work in killing cancer cells before they’re studied in people.
So, how do we know that these new promising treatments are going to be safe or effective in our patients? How do we decide if they are going to be better than, or help to enhance, our existing established cancer treatments? The answer is through clinical trials.
Clinical trials
In the last 40 years, vast improvements have been made in survival rates for children and young people with cancer, largely driven by clinical trials. Clinical trials are vital to carefully studying the effects of new medicines or approaches to treating cancer in children. If a new medicine is shown to work well without too many side effects, it may then be licensed and become available as a routine treatment for patients. The time that it takes for a medicine to be tested, approved and licensed can vary widely. It may take more than 10 or 15 years to complete this process. So, why does it take so long?
Clinical trials generally have three main stages, known as ‘phases 1 to 3’, that must be completed to show a medicine is safe and can work in a certain cancer.
Phase 1 > Trials only test a new treatment in a few people. The aim is to see how much of the treatment is safe to give and the side effects it can cause. If deemed safe, it will be tested in a phase 2 trial.
Phase 2 > Trials test the treatment in more people to continue to find the best dose, collect information on side effects, see how well the medicine works in treating a particular cancer or group of cancers and whether it’s good enough to continue to be tested in a larger phase 3 trial.
Phase 3 > Trials are tested in larger group of patients to test if the new medicine is better than the best existing treatments. These trials are often ‘randomised’, where patients taking part are put into treatment groups at random to be able to compare the new treatment with the best standard treatment.
There are many factors that can influence how long these phases take, as we detail below.
Designing, funding and setting up trials
Clinical trials are designed by a research team which includes clinicians, clinical trials specialists, statisticians and patients, parents and members of the public. It ensures that trials are set up properly and safely, according to strict standards, and that trials meet the needs of patients.
Before the trial can happen, the research team must obtain funding from a research or charitable funding body or a pharmaceutical company. This money is necessary to make the trial possible and is used to fund the new medicine(s), the expertise required to design and manage the trial, the opening and recruiting of patients onto the trial in hospitals, the collection and storing of data about trial patients, and the analysis and reporting on the results. With funding in place, the team can prepare the trial protocol and the regulatory and supporting documents such as patient information sheets. It will decide:
- who can take part in the trial
- what the different treatments are
- an appropriate trial design
- what tests the patients will have
- how the results from the study will be assessed
Once the protocol is finalised, the team will need to get approvals from regulatory bodies. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) must review and authorise the protocol according to strict regulations. Trials must also meet ethical standards to protect the safety and wellbeing of patients who take part and be reviewed by a Research Ethics Committee. Once these approvals are in place, it’s necessary to ensure each recruiting hospital has the appropriate facilities and staff who are trained and able to deliver the trial safely. All these reviews can take many months before it is possible to open the trial.
As children’s cancers are rarer than adult cancers, research teams from several different hospitals and countries have to work together to recruit enough patients onto these trials. This can affect how long it takes to organise the trial and set it up.
What happens next?
Once a clinical trial is open in a hospital, doctors and research nurses can begin to recruit eligible patients into the trial. They must make sure that children and families receive information about the trial and understand what taking part means.
Information about the patient taking part in the trial, and how they respond to the treatment, is collected in a secure database which protects the identity of the patient. To ensure the safety of patients on the trial, processes are put in place for doctors to report any unexpected side effects or reactions to treatment back to the research team. An independent committee will also review the data collected during the trial to make sure it’s safe.
After trial treatment finishes patients are followed-up for some time, usually for several years but this depends on the type of treatment and group of patients. Data collected during the follow-up period will show the research team how well the treatment works over a longer period and allow them to learn about longer-term side effects. Once this follow-up period is complete for all patients on the trial, the research team can analyse the results and determine if the new trial treatment should be used as the new ‘standard of care’ or if further research needs to be completed.
We hope that this has shed some light on how cutting-edge science in children’s cancer is translated into improved patient care, and the importance of clinical trials in pushing boundaries when it comes to research into children’s cancer.
From Contact magazine issue 102 - Spring 2024
