Building resilience in cancer trials

Clinical trials are a cornerstone of oncology research, vital for turning scientific breakthroughs into effective cancer treatments. Despite their critical role, these trials are plagued with an array of challenges and most result in failure – a pressing concern, as cancer claims over 10 million lives each year globally.¹ In the United States alone, the American Cancer Society projects 2,001,140 new cancer cases and 611,720 deaths in 2024.²

These statistics highlight the importance of cancer clinical trials and the urgent need to enhance their success rates. Globally, researchers are making strides to address this challenge and pharmaphorum recently had a conversation with one of them about these efforts.

Deepika Khedekar, a clinical pharmacologist with over 12 years of experience leading oncology and gastroenterology trials for US- and Australia-based pharmaceutical companies, is trying to decode cancer clinical trials. Her research has not only helped reveal insights around challenges that impede the success of cancer trials, but led her to develop the CancerEngage framework, which aims to make cancer trials more robust and efficient. Her work was recently selected for a presentation at the American Society for Pharmacology and Experimental Therapeutics (ASPET) conference in Virginia.

Given your experience leading oncology trials, what are the most significant challenges you've observed that hinder their overall success rate?

Khedekar: Leading oncology trials for over a decade has been a deeply humbling experience. Witnessing the persistently low success rate - a mere 5% - is a stark reminder of the 10 million lives lost globally to cancer each year.

Several key factors contribute to this bottleneck. The astronomical cost of developing a single cancer drug, a staggering $2.7 billion, severely limits the number of trials we can conduct. Furthermore, low participation rates, hovering around just 14% are a significant impediment. The rapid progression of cancer itself plays a role in this. Patients in oncology trials often experience significantly more serious side effects compared to non-oncology trials, leading to frequent dropouts. Finally, oncology trials are notoriously lengthy, taking much longer to complete than non-oncology trials. This extends the timelines for drug development and puts further strain on resources and funding.

These factors create a significant bottleneck, limiting the number of trials conducted and ultimately hindering the development of new cancer therapies.

You mentioned the extended durations of these trials. Can you elaborate on specific aspects of oncology trial design that contribute to these long durations and potentially lower patient participation rates?

The extended duration of oncology trials is a cause for serious concern. Each phase of these trials takes about 14 to 18 months longer than non-oncology trials. This devours significant resources and funding. But here’s the thing: cancer progresses rapidly, and the longer these trials drag on, the more likely we are to see patients drop out, making it challenging to complete these trials successfully.

One major factor contributing to both the long durations and lower participation rates is the issue of strict eligibility criteria. Currently, a staggering 80% of patients don't qualify for these trials, resulting in a meager 14% enrolment rate. This not only limits participation, but also extends trial durations, as finding qualified participants becomes a more challenging task.

Furthermore, these trials often disregard real-world demographics. Many exclude older adults and are solely located in urban areas. This creates skewed data that doesn't reflect the actual cancer population, potentially rendering treatments ineffective for the very people who need them most. These challenges are derailing cancer trials. We need a more strategic and holistic approach.

Given these challenges and the low success rate, what kind of approach do you recommend to modernise cancer trials and improve outcomes?

I think we need to fundamentally rethink the way we design and conduct cancer clinical trials.

This is where the CancerEngage framework comes into picture. It's a structured framework designed to make them more robust, patient-centric, and efficient. Its goal is to elevate trial participation, inclusivity, and participant diversity, while simultaneously boosting operational efficiency and scalability. It addresses various challenges that have historically impeded the success of trials by defining a two-pronged approach.

First, it modernises trial inclusion criteria, introduces diversity benchmarks, and integrates patient-feedback loops to make trials more accessible and representative. Second, it outlines how emerging technologies should be integrated into trial operations to expand reach, increase participation, reduce dropout rates, and enhance transparency, thereby building trust with participants. The ultimate objective of CancerEngage is to ensure that clinical trials are directly aligned with the real-world needs of participants, enhancing both outcomes and overall trial efficiency.

So, cancer trials often struggle with low participation rates, particularly from diverse populations and those that are traditionally excluded from these trials. What approach does CancerEngage propose to address this challenge and increase inclusivity?

CancerEngagesignificantly enhances the design of cancer clinical trials by addressing restrictive eligibility criteria, which traditionally limit participation. It proposes expanded criteria to include a broader spectrum of participants, such as older adults, individuals from diverse genetic backgrounds, and patients with an ECOG Performance Status of 2 - those who can perform self-care, but who may need considerable rest. This initiative ensures that clinical trials are more inclusive and reflective of the diverse populations affected by cancer.

Additionally, CancerEngage is committed to implementing diversity benchmarks in the design of these trials. This commitment is vital for ensuring that the studies are demographically inclusive, which is crucial for achieving scientifically valid outcomes, considering that treatment responses can vary significantly across different groups. In addition, it prioritises patient centricity by incorporating direct feedback from participants into trial design and execution, enhancing alignment with participant needs and improving satisfaction and retention.

Enrolling qualified participants, keeping them engaged, and ensuring smooth operations are critical aspects of a successful cancer trial. Unfortunately, factors like limited outreach strategies and operational inefficiencies often hinder these goals. How does CancerEngage address these specific challenges?

Only 2% to 8% of adult cancer patients participate in cancer trials today and about 20% of these trials fail - solely due to insufficient patient enrolment. CancerEngage aims to address this challenge by weaving emerging technologies strategically into the fabric of clinical trial design. It employs AI-driven platforms to enhance awareness and engagement through tailored, culturally sensitive communication strategies. To extend the reach of trial and scale trial operations efficiently in remote and underserved areas, it integrates drone technology and mobile trial units. This approach not only broadens trial access, but also reduces the logistical costs and resources needed to conduct and execute these trials.

Cancer patients often hesitate to participate in clinical trials due to uncertainties about the processes and potential risks involved. To mitigate this, CancerEngage incorporates virtual reality (VR) simulations into its framework. These simulations provide a detailed and realistic preview of what participants can expect during the trial, clarifying procedures and addressing common concerns. By visually and interactively demonstrating the trial processes, these VR simulations play a crucial role in reducing anxiety and fostering trust among potential participants.

How has the scientific community responded to this approach?

The CancerEngage framework was very well-received at the ASPET 2024 conference in Virginia. Attendees seemed particularly to appreciate how the framework refines trial criteria to inclusively cover broader patient groups, such as those with an ECOG Performance Status of 2 and older adults, ensuring diverse population representation in trials. The integration of emerging technologies to facilitate this process, alongside measures to boost patient centricity, was highlighted as transformative and underscored the necessity for advancing the framework to a second phase of adoption and detailed evaluation, aiming to validate its effectiveness in real-world settings and enhance the robustness and efficiency of clinical trials.

How should research organisations approach the implementation of the CancerEngage framework to effectively manage transitions and challenges?

I envision the adoption process as a four-phased approach. In Phase 1, organisations should focus on comprehensive training for staff to fully understand the framework's goals and vision. In Phase 2, trial designs can be refined to incorporate updated criteria, such as ECOG Performance Status 2 (PS2) patients, diversity benchmarks, and patient-feedback loops. Phase 3 encourages the adoption of advanced technologies like AI, drones, and mobile units to expand trial reach and efficiency.

Finally, in Phase 4, it’s crucial to evaluate the outcomes and optimise the newly integrated trial protocols. Continuous collaboration with key stakeholders - including research teams, technology partners, hospitals, and regulatory authorities - is essential throughout these phases to ensure successful integration and adoption of the framework.

As you look to the future, what are your hopes for CancerEngage, and how do you envision it influencing global clinical research practices?

Looking forward, I'm really hopeful about what CancerEngage can do. The main idea is to make cancer trials better - more inclusive, efficient, and robust. I hope this approach inspires research groups worldwide to see the benefits of modernising these trial methods. I am committed to testing CancerEngage extensively in a diverse clinical research setting, making sure it adapts well to different regulations and needs. Ultimately, my goal is to improve the clinical trial process, allowing new treatments to reach patients faster and more effectively.

About the interviewee

Deepika Khedekar is a clinical trial lead at IQVIA, a global clinical research organisation, where she spearheads clinical trial monitoring programmes for major pharmaceutical companies. In her 12+ years in the pharmaceutical industry, she led phase I, II, and III clinical trial programmes in oncology, gastrointestinal, and respiratory therapeutics, including drugs for leading US- and Australia-based pharmaceutical organisations, 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.