Clinical Research: Phase 1 - Phase 4

Innovations in Rare Oncology Trial Design

A rare cancer is often defined as one with an incidence of less than 15 per 100,000. The patient populations of these conditions are so small that traditional clinical trial design strategies can be unfeasible.

But, with such a low incidence, just why is rare oncology research so important?

Why Rare Oncology Needs Innovation

Keep in mind that the term “rare” can be deceptive. It doesn’t reveal the true public impact of these cancers. This diverse group includes 186 cancer types and makes up 27 percent of all new cancer diagnoses in the U.S. Additionally, rare cancers are significantly more common than non-rare cancers in the pediatric population.

Rare cancers as a whole also have high mortality rates. These conditions are responsible for 20–30 percent of cancer deaths today. They also have significantly lower five-year survival rates at 47 percent vs. 65 percent seen in more common cancers.

High mortality can be attributed to a lack of effective treatment. While many potential drugs exist, few have been developed. In fact, as of 2014 more than 40 percent of US FDA orphan drug designations were for rare cancer therapies.

Current Trends in Rare Cancer Research

Luckily for patients with rare cancers, there is a recent trend towards international cooperation between the pharmaceutical industry, biotech, and academia. Researchers are also making more frequent use of adaptive design. This strategy incorporates prospective planned opportunities to modify the trial based on interim data analyzed at predetermined time points.

In one 2015 paper, the International Rare Cancers Initiative described actions taken in recent studies that may prove appropriate in future rare oncology trials:

  • Accepting greater type I error
  • Abandoning the trial early due to a lack of observed benefit
  • Balancing scientific value and feasibility
  • Incorporating Bayesian elements to quantify the resulting level of information
  • Utilizing multi-arm selection without assumption

Trending Trial Types

These two trial types are being used more often and successfully in rare oncology:

Basket Trials

These trials test the effect of a single drug or drug combination on a specific mutation independent of tumor histology in a variety of cancer types (“baskets”).

Umbrella Trials

This strategy assesses the effectiveness of multiple drugs on an individual tumor type, including different mutations in a single cancer. Patients are randomized by most prominent mutation with drugs selected known to target it.

Putting Innovation Into Practice

The glioblastoma multiforme (GBM) AGILE study is an example of an ambitious project that incorporates a variety of rare oncology research innovations. With global involvement from over 130 researchers across various fields and its use of adaptive design principles, GBM AGILE may have taken some of its cues from agile software development. This umbrella trial incorporates Bayesian statistics to consider information from patient experiences over the course of the trial. Also included in the trial design is the evaluation and validation of biomarkers — there are currently no standard biomarkers available to GBM researchers.

For more information on these and other cutting-edge trial design strategies, check out our recent webinar on rare oncology research.