All agree that ethnic groups are massively under-represented when it comes to clinical trials, and…
Basket trials, along with umbrella trials and platform trials, are classified as master protocols which investigate multiple hypothesis throughout concurrent sub-studies. Rather than using the site of tumor origin for therapy selection, basket trials study a targeted therapy in multiple patient populations in one cohesive design based on common characteristic(s), such as the same molecular abnormality or biomarker that drives tumor growth and progression. This is based on the notion that cancers arising in different organs but with common biology or shared clinical features may respond similarly to targeted therapies. By utilizing these shared characteristics to group subjects into subtypes (or ‘cohorts’ or ‘baskets’), this trial design helps to addresses the “R3”: getting the right therapy to the right patient at the right time.
There are many benefits to this trial design, including: an increased “hit rate”, by enrolling patients with potentially rare molecular characteristics across tumor types; expediting the drug development and evaluation process leading to faster regulatory review compared to traditional trials; enhancing the efficiency of drug development by looking for large effects in small populations; and offering novel therapeutics to a broader group of patients who may benefit. As such, basket trials are becoming increasingly more popular in oncology trials, as well as other indications.
However, considering their inherent complexity due to the inclusion of more than one cancer type within the same trial structure, the logistics involved with the planning, coordinating, conducting, and managing of a basket trial are far beyond that of a traditional trial and present some unique challenges. Thankfully CRAs qualified in oncology clinical trials are in a similarly unique position to address and overcome common challenges with site staff and sponsors to ensure your basket trial is conducted and managed successfully.
Challenge #1: Multiple Patient Populations
Multiple primary disease sites mean multiple patient populations, so subjects with different diagnostic paths, different prior therapies, and different disease presentations may be included within a single cohort. Even qualified oncology CRAs are unlikely to have an in-depth knowledge of every represented cancer type to an equal degree. Thus, CRAs must seek out relevant knowledge to effectively review subject data, such as standards of care and typical disease progression patterns, for each enrolled disease site. Though continuing education and research of approved diagnostic and treatment guidelines are obvious as solutions to this challenge, perhaps the most valuable resource for information is the site staff.
Asking site staff where potential patients referrals are coming from tells the CRA the available patient pool at the site, and whether the site has the patient population to enroll in one, some, or all trial cohorts. Equally important is inquiring with the site-staff about the typical diagnostic and/or treatment path a potential patient usually undergoes before their referral to the site team for consideration for your basket trial. This is important to know as local practice may vary depending on the research center.
These discussions are key to understanding each different population included in the basket trial at a particular site, and should occur on an ongoing basis from feasibility to enrolment closure to ensure any changes to site processes or standards of care are captured. Additionally, relying on the site team’s expertise in treating patients and respecting their role as knowledgeable experts will foster trust between the CRA and site team, and lay the groundwork for mutually beneficial relationships throughout the conduct of the trial.
Challenge #2: Varying Eligibility Criteria and Protocol Requirements
Each cohort for a basket trial has one or more unifying eligibility criteria, such as a specific genomic or diagnostic test, which can have the potential to impact screening timelines. Identifying the key limiting factors with both the sponsor and site staff during the feasibility process is crucial. Experienced, qualified oncology CRAs will recognize this and will ask relevant questions soon after initial contact (‘Is testing done locally or centrally?’, ‘What is the turnaround time for results?’, and ‘Is this test standard of care?’). Obtaining this information from study outset promotes full transparency and establishes realistic timelines to help ensure no unknown delays impact screening and enrolment.
Just as there will be different eligibility criteria for each cohort, there may also be variation in the schedule of assessments, specific study objectives, and scientific rationale for inclusion of each population per cohort. CRAs must have an in-depth understanding of the protocol and the ability to quickly, concisely, and clearly highlight the differences between the cohorts to site teams during site initiation, and on an ongoing basis. Ensuring the channels of communication between the site staff and CRA are open and accessible is a top priority for the qualified oncology CRA as routine protocol retraining or clarifications with the site team may be required to ensure site protocol adherence and trial success.
Challenge #3: Identify Patients and Motivate Sites to Enroll Different Types of Patients
One of the main challenges for sites can be identifying and approaching the right patients for a basket trial. Large research centers may have dedicated disease-site research groups, a single large clinical trial group that sees all disease sites, or a combination of the two. Understanding how the site operates during the feasibility stage is vital in identifying the key people or groups who will be the first point of contact with your potential patient pool. Obtaining their contact information, touching base regularly about challenges in clinic, and inquiring about any pre-screening or screen failure patterns will allow the CRA to cater their help to the site-specific challenge at hand.
Depending on the number of cohorts, unique eligibility criteria, and unique assessments required in one protocol, supplemental materials for site use can be created and used by the site’s staff to identify patients more easily during pre-screening. For example, a laminated note card that lists key eligibility criteria can be created and distributed to site staff. This could be especially helpful at large research institutions that receive referrals and treat patients from large surrounding regions, to help study teams quickly identify potential subjects and determine if further screening is warranted. The key is to remain flexible and only provide supplemental materials to sites that clearly has benefit. It’s equally important to recognize when providing additional study materials is a hinderance (e.g. if a site is enrolling into 1 cohort only).
Qualified Oncology CRAs are Instrumental to Basket Trial Success
Basket trials are effective in accelerating recruitment and expediting the drug development process and regulatory review, when managed and conducted correctly. CRAs can be instrumental to your basket trial success by ensuring there is open and consistent communication with the site teams, remaining flexible as challenges arise, and proactive in identifying potential risks as well as methods of improvement.
Why Work with CRAs from a Niche CRO Partner?
The smaller, niche CRO that is well managed, with low turnover, and a clinical operations team populated with experts in oncology can provide the qualified CRAs needed for the successful execution of your basket trial. At Scimega the same project team follows a Sponsor’s program from Phase I to II, and subsequently heads any scale-up to Phase III that follows. Thereby providing not only the necessary therapeutic alignment of personnel, but also the accessible knowledge of what is and has gone on with a study program from its outset.
In every instance Scimega works with your team to devise innovative solutions to address your unique challenges, bringing together the right combination of specialized expertise for your cutting-edge oncology trial. If you’re interested in learning more about the Canadian opportunity, explore an expansion with us!
Contributed by: Sarah Young, Senior Clinical Research Associate