Things to Remember When Planning Your Phase I Oncology Study

Oncology trials are complex, especially first-in-human phase I trials. You are full of optimism, while at the same time anxious about all of the unknowns. Important questions about the drug’s safety profile, pharmacokinetics, and dose need to be answered. As you start planning for the phase 1 study, you may quickly realize how much more complex these uncertainties make the management of the study. The key to success is understanding and managing the risks.

We always recommend to sponsors that they use a CRO that is highly experienced in oncology trials to guide them through all of the nuances that will inevitably occur in the study.

However, many of these oncology CROs focus exclusively on phase II-IV trials. Should you consider them for your phase I oncology study?

Possibly, but proceed with caution.

Many CROs avoid focusing on phase I oncology trials due to their shorter timeframes, lower budgets and uncertainties.

Profile of a Phase I Oncology Study

Phase I trials typically include 15 to 30 patients to determine the maximum tolerated dose (MTD) or optimal biological dose (OBD). The patients are enrolled into small groups, or cohorts. There are typically two to three investigators involved. The first cohort receives the initial dose of the new drug, which is based on previous animal studies, and both the investigator and CRO monitor the patients for dose-limiting toxicities (DLTs). If there is an acceptable level of toxicities, then a new cohort receives a higher dose of the same drug. The dose is then increased in increments with each new cohort, until the investigators find the MTD with an acceptable level of toxicities. This MTD is used in further testing.

4 Keys for Finishing Your Study on Time and on Budget

Phase I Oncology StudyHere are the elements that can affect the quality of data you receive during the study and the overall study costs:

Site selection. Has your CRO selected the right mix of sites to meet the patient enrollment timelines? Large academic institutions often have well-respected investigators, but require a lot of administrative work to get the site up and running. If you’re solely relying on large academic sites, your overall timeline may be longer than what you’ve budgeted for. And if your CRO doesn’t have a close working relationship with the sites, it will most likely take them longer to complete all of the administrative work than it would if they had an established working relationship with the site.

Site sequencing. The use of cohorts creates a linear timeline; the next cohort cannot start until the results of the previous cohort are obtained. This creates pressure to get the first cohort(s) enrolled efficiently at the beginning of the timelines. Many large academic centers cannot enroll patients quickly enough due to the administrative work required (see above), so it’s important to use the sites with the least amount of setup time required for the initial cohorts, so the study gets underway while the other sites are getting up and running.

DLTs. The management, CRA, medical monitor and safety associate should be well versed in phase I studies in order to understand how DLTs affect cohort management. The rate of DLTs determines the number of patients at each dose level; therefore, close monitoring and communication with investigators are critical.

Adapting to changes in real time. When the inevitable issues arise, they typically cause a cascading effect: a change in a single decision can require changes in other areas of a trial. Check with your CRO to ensure that their team can adapt to these changes in real time. Because of the small size of the typical phase I oncology study, many project teams at large CROs that do not have extensive phase I experience require a long time to adjust the timelines and workflow. This can extend your timelines and possibly your final cost. (Bid transparency can help to mitigate this.)

Having your CRO as a true partner on your study, instead of simply an outsourced team of researchers focused on executing tasks, is the best approach for obtaining the data you need on-time and on-budget.

Ask your CRO how they’ll handle the above issues, and you’ll be better able to select the right CRO for your phase I oncology trial.