Matthias Weiss, MD
Chair, ECOG-ACRIN Community Cancer Committee
Medical Director for Research, ThedaCare

Kristin Wenzel, PharmD
Investigational Drug Service and Oncology Pharmacist, ThedaCare

Amy Squire, RN, BSN
NCI Clinical Trials Manager
Metro-Minnesota Community Oncology Research Consortium

An increasing number of National Cancer Institute (NCI) National Clinical Trials Network (NCTN) therapeutic trials are directed toward rare disease presentations. These include trial interventions targeting subsets of patients with disease presentations defined by rare pathology (e.g., EA6174/STAMP in Merkel cell carcinoma or EA2205 in combined hepatocellular carcinoma-cholangiocarcinoma) and, increasingly, defined by specific molecular targets (e.g., the ComboMATCH treatment trials). The probability of encountering eligible patients for such trials is low. It may be one or none for any given study over the course of a year at an NCI Community Oncology Research Program (NCORP) site like ThedaCare with 3000 new analytical cases of cancer per year. Given limited financial resources, the opportunity to make such trials available to our patients is restricted.

In this article, we include two “how to” perspectives on facilitating just-in-time (JIT) access to NCTN therapeutic trials. The first is from ThedaCare, a component of the Wisconsin NCORP. Then, we describe the perspective of the Metro-Minnesota Community Oncology Research Consortium (MMCORC). We hope readers will find these approaches of value and that, by sharing the information, additional community-based sites will consider establishing such a program.

Just-in-Time Trial Facilitation at ThedaCare: A Step-by-Step Guide (Dr. Weiss and Dr. Wenzel)

NCTN therapeutic trials that have a low accrual potential (defined as < 5 patients per year) and offer a possibly beneficial therapeutic intervention may be eligible for our JIT Clinical Trial Portfolio. The process is as follows:

• During the routine feasibility evaluation process of selected NCTN trials, the assigned research team, including the disease-specific principal investigator, determines whether it is feasible for a trial to be listed in the JIT portfolio.
  • The research team considers factors such as technical requirements, validation procedure requirements for technical equipment, biospecimen sample requirements, electronic medical record (EMR) treatment plan build complexities, and drug administration complexities.
• Routine screening of patients for trial eligibility includes both currently open studies and JIT studies listed in the portfolio.
• When a patient is identified as a potential candidate for a JIT trial—and after patient and care team interest is confirmed, the research team rules out any insurance barriers to trial participation, and the local principal investigator verifies eligibility.
  • At this point, the JIT trial is opened for the patient.
• Institutional review board (IRB) approval is facilitated by delegating IRB oversight to the NCI Central Institutional Review Board (CIRB) for NCTN trials, which is the standard for our institution. NCI CIRB approval is typically accomplished within 3 working days.
• Implementation of a trial-specific treatment plan, trial-specific educational requirements, and any other research procedures are accomplished according to the plan initially developed during the feasibility assessment. In nearly all instances, investigational therapeutic intervention for a patient enrolled in a JIT trial will take place less than 1 week from opening the trial and registering the patient.
• Our current JIT pharmacy process is to build out trial/investigational product (IP)-specific drug records for each sponsor-supplied IP to assure transparency within the EMR, correct drug selection/compounding, and to avoid charges to the patient.
  • These build requests are prepared when JIT status is determined—and expedited once we have an eligible patient for a JIT trial. The requests are built/validated within 2-3 business days.
  • The Investigational Drug Service (IDS) pharmacist will then edit a pre-built and validated commercial BEACON plan (as similar to the trial protocol as possible) to align with protocol requirements and to include the trial/IP-specific drug records. The prescribing investigator and the research nurse review this edited plan to ensure proper build prior to treatment.
• Once a JIT trial has enrolled a patient, we subsequently list it as ‘open’ in our Clinical Trial Portfolio.

Just-in-Time Trial Facilitation at Metro-Minnesota Community Oncology Research Consortium: A Step-by-Step Guide (Ms. Squire)

As trials become more specific with smaller, targeted patient populations, Metro-Minnesota Community Oncology Research Consortium (MMCORC) has also started evaluating the resources and effort required to open a trial as usual versus assigning a trial the JIT designation. The steps are as follows:

• The JIT trial process starts with our Scientific Review Committee (SRC), which assesses the scientific merit of a study and decides whether to open it within our consortium. When a study is presented with a rare pathology or the patient population is seldom seen in our community oncology clinics, the SRC discusses whether it should be opened following our usual practice or if it should be a JIT trial.
  • Considerations in this discussion include pathology/disease type, volume of potential patients, and potential for eligibility.
• Once the SRC decides to move forward with a study, but assigns it JIT status, we utilize the following process to communicate the trial’s availability (and open it once a participant is identified):
  • JIT trials are listed on our main protocol list, and the protocol is made available to our team members through our MMCORC website. We include verbiage on our protocol list and our website alerting team members that it is a JIT trial and to contact the program manager for the study immediately if a patient is identified.
  • Site team members routinely screen for patients, and JIT trials are included on the portfolio lists given to site team members and providers.
• Once a patient is identified and their initial eligibility is confirmed, depending on the pathology, we may ask the team members to confirm with their pathology department that the patient meets any pathology requirements (e.g., EA2205).
• After eligibility is confirmed, MMCORC institutes an ‘all-hands-on-deck’ approach, aiming to put the patient on study within about 2 weeks of the initial team member inquiry.
  • Note: A critical part of this process is communication between sites and our main office, which handles all our regulatory needs and clinical trial openings.
• MMCORC utilizes the NCI CIRB for oversight, which allows for faster processing of required forms.
  • The regulatory process usually takes about 24-48 hours to complete, as our regulatory specialist only focuses on the healthcare system in which the patient was identified.
  • If a study is a Delegation of Tasks Log (DTL) trial, we make sure to roll out the DTL as soon as our regulatory team member processes all IRB documents. Sites are kept up to date on document processing and DTL status.
  • Once available, consents are usually emailed directly to team members.
• Since we work within seven health systems, EMR treatment plan builds vary from site to site. At a site level, team members are responsible for building the protocol within their respective EMR. Still, the program managers and our regulatory specialists make sure to send all required documents needed: protocol, pharmacy manual, lab manual, and funding sheets. Usually, site team members will start the EMR build as soon as they know a patient is initially eligible and the provider and patient have confirmed interest.
• MMCORC utilizes CREDIT as our Clinical Trial Management System (CTMS). Once our program managers are alerted to a potential patient, they communicate with our CREDIT specialist to start the build.
• Most patients can start treatment on a JIT trial within 2-3 weeks.
• Once the JIT trial is open at one site, we work to open it at all other eligible consortium sites.

The most important factor in making a JIT trial work is communication between all personnel: site teams (including enrolling investigators), regulatory specialists, program managers, CREDIT specialists, and any others. Clear and defined processes for opening trials, such as checklists, are also helpful and can prevent items from being forgotten or overlooked.