Blogs

Demystifying cancer clinical trials for patients

19 Nov 2021

CellCentric has been collaborating with Prostate Cancer Research (PCR) to better understand the views of people with cancer.  It is also an opportunity to share with patients the processes and challenges of discovering and developing drugs. 

Andrew, Nigel and Steve delivered a recent webinar to PCR to help explain how academia and industry progress a concept for a new cancer therapy from the lab, through clinical trials, to something widely available in hospitals.

 

Cancer is highly prevalent; one in two of us will get cancer in our lifetime.  Every day a cell in a body becomes cancerous, but most of these are quickly countered by our immune systems.  The disease comes in many different forms, with some 200 different classifications of cancer. Therapies do not need to kill every last cell; the body also plays a part.  If the dominant clone of cancerous cells is tackled, the immune system can play its part in keeping the disease in check.   

Developing novel cancer drugs takes long timelines and deep resources, over $1bn on average.  Despite that, there are over 900 new potential anti-cancer treatments currently in development.  Attrition rates are high; of novel drugs that enter clinical trials, only 1 in 10 make it all the way through to the market.

Physicians and companies running clinical trials are obligated to register cancer studies on a public register, such as www.clinicaltrials.gov.  For patients this is a fantastic resource, enabling anyone to search studies by cancer type and by geographic location.  The requirements to enter any study is provided; specifically the inclusion and exclusion characteristics that make a person eligible for each trial.   Patients have the opportunity to be equally informed on new trials as their doctor or oncology specialist and are encouraged to discuss with their treating physician any clinical trial for which they think they might be potentially suitable. 

The UK is well placed for exploratory early stage clinical trials.  Since 2007 there has been strong push by government, partnering with charities such as CRUK, to establish a network of inter-linked Experimental Cancer Medicine Centres (ECMC).  90% of the population are within 50 miles of such a hub, which have a strong focus on driving the development and delivery of new medicines.

Phase 1 clinical studies focus on understanding three key aspects: 1) Primarily they are to characterise safety and tolerability.  Additionally 2) pharmacokinetics are investigated; how a drug is available in the body, how it is metabolised and 3) pharmacodynamics; what the drug does to the body. 

Prior to patients being dosed, pre-clinical studies in animals pick up around 70% of major toxicities seen in patients.  That still leaves a significant proportion where testing in patients is required to see how safe a drug is likely to be in the long term. Phase 1 usually entails a gradual escalation in overall drug dose, before a recommended Phase 2 dose and schedule is defined (RP2D). Subsequent studies focus more on disease impact, anti-tumour effectiveness and overall response rates. 

Phase 2 and Phase 3 studies often compare the new treatment with a placebo control, or against existing standard of care agents.  When a drug is clearly better than existing available treatment, data is then submitted to regulators for a market authorisation for general use.  Additional data is also gained to investigate cost effectiveness of new therapies, managed in the UK via NICE (National Institute for Health & Care Excellence).

Not all patients are the same; there is significant difference in personal susceptibility to particular cancers, as well as variation in disease progression in different people.  Some of these differences can be picked up by profiling people’s DNA, and characterising samples from tumours themselves.  Drugs can be specifically matched to patients and tumours with certain mutations (genotype) or over-expression of certain proteins (phenotype).  This type of biomarker analysis is now a significant part of any clinical trial campaign. Genotype and phenotype profiling can improve the effectiveness of drugs ten-fold.  Looking forward, this type of targeted strategy for patients will become ever more prevalent.

Clinical trials are highly regulated; in the UK by the MHRA, in the EU by the EMA and in the US by the FDA.  All trial protocols and procedures have to be approved in advance of any dosing of patients.  They also have to have a defined, accountable lead clinical investigator; for CellCentric’s prostate cancer trials with our drug CCS1477, this is Prof Johann de Bono in the UK and Prof Kevin Kelly in the US. 

Additionally local ethics committees review what is proposed, and are key in helping ensure that documents such as the Informed Consent Form adequately explain to patients the details of the trial, what potential risks are associated with taking part, and the alternative options available.  They check that all patient documentation is clear and understandable to a non-specialist. 

Once a trial is underway, there are regular Safety Review Committee meetings, where all doctors associated with each trial discuss ongoing patients and can flag up positive and negative findings to all, as expediently as possible.  The Safety Review Committee may then recommend modifications to the trial based on emerging data.

Developing a novel drug is motivated by addressing the needs of patients, doing something that is not achieved by existing therapies and care packages.  It is to improve the outcome for patients and quality of life overall.  By listening to patients on studies, drug developers can learn and adjust how things are run.  They can also pick up on softer measures of anti-tumour effects, such as reduced pain and general well-being, quality of life.  As trials progress into Phase 2 and 3, continuing to engage with patient reported outcomes is important, through diaries, Apps, focus groups, and one to one interviews.

For CellCentric patient engagement has already influenced the language used to explain our trials, and has helped ensure that things are kept as simple as possible, for instance with scheduled visits to hospital.  The fact that CellCentric’s clinical trial drug is an oral capsule has proven to be really appreciated by patients. 

 

CellCentric summary

CellCentric is focused on developing CCS1477 for the maximum benefit of cancer patients, as expediently as possible.  CCS1477 is a small molecule that inhibits p300/CBP, two proteins that drive the expression of certain genes that drive tumour progression.  The drug and its mechanism of action have evolved from a deep research in epigenetic-related processes.  The company is highly science driven, but is balanced with being very much focused on patients; ensuring that CellCentric meets the needs of people with cancer, delivering something not currently addressed by existing therapies and care.

Prostate Cancer Research summary

Prostate Cancer Research (PCR) is a patient-centric research and information provision charity that is dedicated to improving and saving lives by both developing new treatments for advanced prostate cancer and empowering people living with prostate cancer. By funding research projects that matter to patients, it is working towards breakthroughs in the prevention, diagnosis and treatment of advanced prostate cancer, and better quality of life outcomes for patients. 

PCR's patient engagement activity is focused on informing and empowering patients about prostate cancer, treatment options and side-effect management through providing the latest clinically-accurate disease information to its patient community and gathering real-life evidence from people living with prostate cancer to enable better insights into their lived experiences. From August 2021 to January 2022, PCR has been hosting its patient-focused 'Living Well with Prostate Cancer Webinar Series' that looks at addressing the challenges patients face and their support needs, particularly with regards to some of the issues that the COVID-19 pandemic have highlighted. For more information, please visit: https://www.prostate-cancer-research.org.uk/living-well/