Phase 1 Oncology Trials Uniquely Challenging for Sites, Experts Say
Close sponsor contact, rapidly moving targets and timelines, unique facility and staff needs — these are only some of the factors that can make phase 1 trials more challenging for sites than the other phases, say several oncology research experts who offer advice for sites considering signing up for early-stage research.
“Phase 1 trials are more intense than phase 2/3/4 trials, and it’s essential that you enter into them with eyes wide open,” says Ann Lovelace, director of research operations at Comprehensive Cancer Centers of Nevada (CCCN).
Phase 1 oncology trials have their own unique challenges, but that shouldn’t deter sites from considering them, Renee Smith, Janssen’s head of early development oncology capabilities and alliances, explained during the MAGI West conference in Las Vegas.
They serve as potential therapies for patients who have little to no other options and offer interesting scientific opportunities for physicians, Smith said. They provide early access to new compounds and experience on safety profiles/adverse event treatment. And they offer higher-enrolling sites the chance to be part of publications and presentations.
But sponsors of phase 1 trials have high expectations, and it’s important that sites are able to keep up with them, she said. In particular, when it comes to data entry and study startup, sponsors will expect sites to move fast as they determine whether the drug is viable for phase 2. And sites that are chosen for dose-escalation studies will be under even more pressure to get trials up and running in a timely fashion, she noted.
“It’s all about how fast can we make a decision on this drug, what are we doing with it? We want to figure this out as quickly and safely as possible,” Smith said. “We want to be sure that when we place the molecule at a [site], they have all the right pieces and parts in place in order to provide appropriate oversight for those patients.”
Open, continuous communication from site to sponsor is critical in phase 1 cancer trials, she added, and sites will be expected to consistently give direct updates. To Smith, this may be the most important element from the sponsor’s perspective and investigators that can’t operate in this way are probably not the right picks for heading these trials, she said.
“Call our physician. Call our study team. It’s such an early phase of the drug — we’re really concerned about the safety and we want to make sure that we’re keeping an eye on things,” she said. “I can’t stress that enough. The engagement and communication is key.”
With these things in mind, sites should evaluate their staffing capabilities/setup for these trials. First, select an overall physician leader for your phase 1 trial program, advised AnaArlene Ramirez, a phase 1 research operations manager at CCCN. This director should be an experienced, motivated researcher who is qualified to oversee the program and its day-to-day activities across the site and advocate for the program itself.
In addition, a site should also have a phase 1 research operations manager — Ramirez’s position — who works closely with physicians on patient cases, prescreening, screening, staff/resource management and reviewing potential trials.
There should also be a dedicated research assistant backing up the physician leader on oversight. This important position helps assess trial opportunities, pick feasible trials and assign clinical research coordinators (CRC) to lead them. But equally important is the support they offer on managing phase 1 complexity; CCCN uses its assistant to manage the many ancillary procedures these trials involve.
“There are so many requirements — serial requirements for collections, EKGs, a lot of times patients have to go and have a biopsy — all of these ancillary procedures are very important,” she said. “Procedures are delegated to our research assistant who makes sure that all these are coordinated and all of the required serial procedures are collected and processed on time as required.”
CCCN also selects CRCs to lead each individual trial. The dedicated research assistant helps with selection and determining how many CRCs are needed for the phase 1 oncology program by considering the number of trials the site is running, the complexity of the trials and the frequency of patient visits.
In addition, it’s important to have experienced pharmacy staff, including a research pharmacist and research pharmacy techs, and involve them from the beginning, Ramirez noted. CCCN makes it a point to bring its dedicated research pharmacist in at the trial feasibility process to ensure nothing important is missed.
A point person should be designated to communicate with the sponsor and keep track of changes, of which there will likely be many (in the form of amendments and protocol clarification letters). Sites should ensure that these changes are covered in the budget so they are reimbursed, as they’ll require time and training on part of the site. The regulatory demands of phase 1 oncology trials can be so significant that some sites use dedicated and backup regulatory coordinators.
It’s also essential to assess sites to ensure they have what is needed for phase 1 oncology research. CCCN has seven locations in the Las Vegas valley but intentionally conducts phase 1 cancer trials at a single site. Dedicated waiting rooms and long clinic hours — possibly even round-the-clock capabilities — will likely be needed, and this won’t be possible for all sites. Some procedures may be conducted many hours after dosing, for instance, so participants may need to wait at the site all day and will require a separate space to do so. Additionally, be aware that some trials will be even more intensive and require 24-hour or multiple-day inpatient admission for observation.
These requirements may not always be obvious in the protocol, said Lovelace. Sites should carefully review every phase 1 protocol, digging down even into the footnotes, to make sure there are no deal breaking surprises, she advised.
“Make sure to review it all — a requirement for an overnight stay that is required of a community clinic can be a deal-breaker,” she told CenterWatch Weekly. “We once reviewed a protocol that required subjects to exercise after treatment by walking up and down stairs. Our clinic is on one floor, so we had to decline. Had we not seen this at that point, continuing to open the trial could have been a waste of time for all involved.”
Participant safety is paramount, as always, and the fact that these trials are evaluating new drugs and molecules is critical to keep in mind, especially when the safety profiles aren’t yet understood. The lead CRC of a trial should have a management strategy in place for reactions, and rescue medicine should be ready. Ask: who will report to the investigator, who will stay with the patients and monitor them until they’re stable and who is responsible if patients must be taken to a nearby hospital or emergency room? Sites should be prepared for many more hospitalizations and serious adverse events in phase 1 oncology trials (and account for this in the budget). CCCN gives out a hotline card to each participant with an on-call phone number for patients that have to go to the hospital.
Compensation is also important for phase 1 oncology trials, especially for community practice programs that don’t have the in-house capabilities academic programs may have. A lot of outside vendors are used by community practices for phase 1 procedures, and it’s important that the use of these is compensated well by the sponsor. Equally important is building relationships with vendors, which may include cardiology, ophthalmology, interventional radiology, biopsy and pulmonary service providers. In working with these vendors, establish hotlines and make clear you’re running phase 1 cancer trials, stressing that time is of the essence.
At the end of the day, phase 1 trials are a much different animal than later stages, and sites that decide to take them on need to be keenly aware of their own capabilities and the asks of the protocol.