Are We Doing Enough to Save Lives in Oncology Clinical Trials?

Each year, 9.6 million people die globally due to cancer, according to a report published by the World Health Organization.¹ To put it into perspective, that's equivalent to the entire population of Switzerland—a startling reminder of the magnitude of this global health crisis. Recent findings from the American Cancer Society paint a distressing picture, with 1.9 million new cancer cases diagnosed and 609,360 deaths recorded in the United States alone in 2022.² Although clinical trials may hold the potential to reshape the trajectory of cancer globally, it's crucial to understand the nature of cancer and its established causes.

The human body is composed of trillions of cells, each with the ability to grow and multiply through a process called cell division. Under normal circumstances, human cells undergo this process to replenish the body with new cells as needed. Aging or damaged cells are expected to die off, making way for fresh replacements. However, this orderly process can go awry, leading to the unregulated proliferation of abnormal or damaged cells. These anomalous cells can form tissue masses known as tumors, which can exhibit either malignant or benign behavior. Malignant tumors, also called cancerous tumors, have the ability to infiltrate nearby tissues and metastasize, giving rise to new tumors in distant sites within the body. In contrast, benign tumors do not invade nearby tissues but can grow to significant sizes, sometimes posing life-threatening risks, such as in the case of benign brain tumors. Cancer can cause a range of disruptive symptoms, from high fever to uncontrolled bleeding, severe weight loss to unbearable pain. Therefore, it is crucial to understand the current state of oncology trials.

Technology, business, clinical trial, science image | Image credit: photon_photo - stock.adobe.com

According to data from the WHO International Clinical Trials Registry Platform (ICTRP), the number of registered clinical trials in oncology has steadily increased over the years. In 2013, approximately 19,211 trials were registered in this field, and by 2022, that number had grown to 26,396.³ Recent years have witnessed numerous breakthroughs in oncology clinical trials, spanning immunotherapies, precision medicine, gene therapy, and combination therapy.

One notable example is a clinical trial conducted by Memorial Sloan Kettering Cancer Center in 2022, which involved rectal cancer patients with a specific rare genetic mutation.⁴ The goal of this trial was to help patients overcome rectal cancer while preserving their quality of life. The trial aimed to eliminate tumors solely through the use of immunotherapy, avoiding the life-altering consequences of surgery, radiation, and chemotherapy. Astonishingly, all 18 participants in the trial experienced the complete disappearance of their rectal cancer—a result never before seen in cancer research.⁴ This extraordinary outcome has generated global interest and provides hope for a new therapeutic avenue for various cancer types with similar genetic mutations.

Another recent example is the research that recently culminated at Yale University with a significant breakthrough for cancer treatments. Although normal tissues like skin or lungs typically have the correct number of chromosomes in most cells, cancers often exhibit aneuploidy—an abnormal chromosome count. The role of extra chromosomes in cancer has remained unclear, leading to uncertainty about their causation. However, the advent of a gene-editing technique called CRISPR empowered Yale researchers to eliminate these chromosomes from cancer cells and halt tumor growth.⁵ Additionally, they identified overexpressed genes associated with these extra chromosomes as potential treatment targets.⁵ Although further research precedes clinical trials, this clinical research study brings hope for advanced, precision-focused cancer therapies.

Furthermore, in a recent breakthrough, scientists from the University of Glasgow and Cancer Research UK's Beatson Institute have made a remarkable stride in comprehending the mechanisms underlying the immune system's inability to recognize and eliminate bowel cancer cells,⁶ signifying a pivotal moment in cancer research. Their research revealed that bowel cancer cells manipulate immune cells, preventing them from perceiving the cancer as a threat and allowing it to proliferate unchecked. By identifying the specific mechanism used by cancer cells to disable immune cells, the researchers hope to develop treatments that can reverse this process.⁶ If a drug can be found to re-engage the "blinded" immune cells and make them see cancer again, it could lead to an effective new approach to treating bowel cancer, the second most common cause of cancer death in the UK.⁶ This breakthrough has the potential to significantly accelerate the clinical trials targeting bowel cancer.

Although numerous recent examples in oncology clinical trials demonstrate the significant role clinical research plays in the diagnosis and treatment of various types of cancer, there are risks and challenges these oncology trials encounter on a daily basis that cannot be overlooked.

Challenges in Oncology Clinical Trials

Firstly, oncology clinical trials target specific types of cancers based on genetics, which makes it challenging to find patients who qualify. The strict pre-screening process means that a significant number of patients, such as approximately 80%in the case of advanced non-small-cell lung cancer,⁷ do not meet the criteria for the trials. This leads to difficulties in recruiting enough participants within the desired timeframe, as seen in 86% of those trials failing to complete recruitment as planned.⁷ Due to the substantial reliance on individual genetics, precision medicine requirements result in the enrollment of only 14% of screened patients in oncology trials, whereas non-oncology trials enroll 54% of the patients screened.⁸

Additionally, low- or middle-income countries struggle with funding, resulting in a significant disparity in the number of clinical trials conducted. High-income countries have over 100 times the number of clinical trials per capita compared to low-income countries.⁹ Limited resources at smaller research sites make it difficult to collect sufficient data, and finding experienced staff to handle complex oncology protocols presents a challenge. The involvement of multiple international sites creates additional complexities in trial management and varying regulatory requirements across countries also impact study start-up times.

Other challenges for cancer clinical trials include a lack of mentorship within the scientific community, poor disease representation, and difficulties in collaborations. Although there are high risks and complex challenges that impede the progress of cancer clinical trials, there are steps we can take to address these challenges and unlock the pathway of life for 9.6 million people who die each year due to cancer.

Solutions to Address These Challenges

Patient recruitment and screening is one of the major challenges for oncology clinical trials due to the strict screening process and complex eligibility criteria. However, modern technology such as the Deep Learning Clinical Trial Matching System (DLCTMS)¹⁰ provides a potential solution. Sponsored and launched by the National Cancer Institute(NCI) in partnership with Columbia University in 2020, the DLCTMS is an oncology-based clinical trial recruitment tool. This software platform leverages artificial intelligence to digitize inclusion/exclusion criteria and analyze potential barriers to enrollment, enabling real-time, objective pre-screening.¹⁰ NCI utilized the DLCTMS to optimize patient matching, starting with 3 trials within its National Clinical Trials Network. The results have been remarkable, demonstrating significant improvements in efficiency and patient participation. Nurses now spend only 17 seconds to screen multiple trials compared to the previous average of 45 minutes per patient.¹¹ The streamlined process has also reduced the time for patient consent and enrollment from up to 48 hours to mere minutes11. Within a 6-month period, the DLCTMS successfully matched patients to over 111 studies with a 90% success rate, showcasing its ability to accelerate and optimize clinical trial recruitment.¹¹

International collaboration is another golden pathway for clinical trials that are dependent on specific genetic requirements. Conducting trials across larger regions and multiple countries expands the participant pool and increases diversity. Modern clinical trial operations platforms incorporating digital compliance, video calling, remote monitoring, and artificial intelligence (AI)-enabled diagnostics enable seamless information sharing among different countries. To address funding challenges, sponsors can utilize remote monitoring platforms and initiate trials in low-income countries, thereby achieving a balanced geographic distribution of trial sites. Collaboration among regulators from different countries becomes crucial to harmonize regulations and ensure equitable access to life-saving drugs.

Furthermore, to address funding challenges, sponsors can utilize remote monitoring platforms and initiate trials in low-income countries, thereby balancing the geographic distribution of trial sites. Leveraging remote technology such as electronic Investigator Site Files (eISFs) enhances efficiency, data collection, and remote monitoring, leading to improved patient care and trial management. By enabling international collaboration, embracing technology, promoting standardization, and recognizing the urgency associated with cancer, we can alleviate some of the challenges and risks inherent in oncology trials.

The landscape of clinical trials in oncology is rapidly evolving, driven by increasing research efforts and advancements in the field of clinical research. The integration of modern techniques, such as CRISPR gene-editing, immunotherapy, precision medicine, and AI-enabled clinical trial operations system has the potential to transform the very fabric of oncology clinical trials and optimize treatment outcomes.

However, amidst this wave of possibilities, we must not forget the somber reality that unfolds each year. The harsh truth is that 9.6 million lives are claimed by cancer each year.¹ The lives that hang in the balance are not mere statistics—they are our loved ones, our neighbors, and our friends. In the face of this immense challenge, we must join forces internationally, establish global standards, harmonize regulations, and raise awareness to confront the risks and obstacles that impede progress in these crucial trials. We can do more to save these precious lives.

Deepika Khedekar, MPharm, is a clinical trial lead at IQVIA Inc, a global clinical research organization, where she spearheads clinical trial monitoring programs for major pharmaceutical companies. In her 12+ years in the pharmaceutical industry, she led phase 1, 2,and 3 clinical trial programs in the respiratory and gastrointestinal therapeutics and drugs for leading US and Australia-based pharmaceutical organizations, such as Gilead Sciences, Macleods Pharma, Arrowhead Pharmaceuticals, NoNO Inc., EpimAb, and Impact Pharma. She started her journey in the field of pharmaceutical research at Pfizer and holds a master’s degree in pharmacy from the University of Mumbai.

References

1. Cancer. World Health Organization. Accessed July 10, 2023. https://www.who.int/health-topics/cancer#tab=tab_1

2. Cancer Facts & Figures 2023. American Cancer Society. Accessed July 10, 2023. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf

3. International Clinical Trials Registry Platform (ICTRP). World Health Organization. Accessed July 10, 2023. https://www.who.int/clinical-trials-registry-platform

4. Piersol B. Trhe Rectal Cancer Clinical Trial at MSK That Changed Everything for Its Patients. Memorial Sloan Kettering Cancer Center. March 6, 2023. Accessed July 10, 2023. https://www.mskcc.org/news/rectal-cancer-clinical-trial-msk-changed-everything-its-patients

5. Potential Breakthrough In Cancer Treatment By Targeting Extra Chromosomes. News release. Yale University. July 7, 2023. Accessed July 10, 2023. https://scienceblog.com/538648/potential-breakthrough-in-cancer-treatment-by-targeting-extra-chromosomes/

6. Barker D. Bowel cancer treatment breakthrough as scientists solve immune system mystery. Independent. June 20, 2023. Accessed July 10, 2023. https://www.independent.co.uk/news/uk/bowel-cancer-immune-system-uk-b2360567.html

7. Liu R, Rizzo S, Whipple S, Pal N, Pineda AL, Lu M, et al. Evaluating eligibility criteria of oncology trials using real-world data and AI. Nature. 2021(592):629-633. doi:10.1038/s41586-021-03430-5

8. Emerging Challenges in Oncology Trials: Enrollment, Protocol Deviations, and Growing Data. WCG. Accessed July 10, 2023. https://www.wcgclinical.com/insights/emerging-challenges-in-oncology-trials/

9. Tang M, Joensuu H, Simes RJ, Price TJ, Yip S, Hague W, et al. Challenges of international oncology trial collaboration—a call to action. British Journal of Cancer. 121,515-521(2019). doi:10.1038/s41416-019-0532-4

10. SBIR Phase I Topic 410 – Cancer Clinical Trials Recruitment and Retention Tools for Participant Engagement. SBIR STTR. 2020. Accessed July 10, 2023. https://www.sbir.gov/node/1944589

11. Definitive Contract 75N91020C00016. GovTribe. Accessed July 10, 2023. https://govtribe.com/award/federal-contract-award/definitive-contract-75n91020c00016