ASCO and Friends Commend FDA for Draft Guidance for Broadening Clinical Trial Eligibility Criteria

May 8, 2019

ASCO and Friends of Cancer Research (Friends) have commended the U.S. Food and Drug Administration (FDA) on four recently released draft guidance documents related to expanding clinical trial eligibility in a joint letter to Acting Commissioner Ned Sharpless, MD.

In the letter, the two organizations note that they “appreciate FDA’s leadership in release of these guidance documents to encourage researchers and sponsors to broaden eligibility criteria and provide sound scientific rationale for decisions to limit opportunities for trial participation.” They also applaud the agency’s “recognition that:

‘some eligibility criteria have become commonly accepted over time or used as a template across trials without a clear scientific or clinical rationale or justification. In other cases, eligibility criteria can be deliberately restrictive, even though it is not clinically merited.’

The FDA guidance documents send the strong message that this practice must change.”

ASCO and Friends supported the FDA’s work on the draft guidance documents by providing suggested guidance language. ASCO and Friends’ collaborative work dates back to recommendations issued in October 2017. The recommendations encourage broader eligibility criteria for cancer clinical trials related to:

  • Brain metastases: The incidence of brain metastases is increasing in specific cancers, particularly affecting patients with melanoma and cancers of the lung and breast. Excluding patients from clinical trials may mean under representing one-half to one-third of patients with certain types of cancer.
  • HIV/AIDS, Hepatitis B, and Hepatitis C: Expanding cancer clinical trial eligibility to be more inclusive of patients with managed HIV, Hepatitis B virus, or Hepatitis C virus infections is justified in most cases and may accelerate the development of effective cancer therapies for patients with these chronic viral infections.
  • Minimum age: Greater understanding of the molecular causes of cancer and the similarities of these causes across pediatric and adult cancers provides greater rationale for including children early in oncology clinical trials. Additionally, when clinical trials are undertaken well after extensive testing in adults, potentially promising new therapies are delayed in reaching pediatric patients.
  • Organ dysfunction: Patients with organ dysfunction are often excluded from clinical trials, regardless of specific drug metabolism or clearance mechanisms. However, as the general population is aging, there is an increasing number of patients with renal disease, hepatic dysfunction, and cardiac disease who also develop cancer. If a drug does not directly affect particular organs or when organ dysfunction does not directly impact drug metabolism or clearance, patients with decreased organ function could participate in a trial. In addition, as data on toxicity become available during drug development, protocols should be revised to include patients with compromised organ function where safe parameters have been determined.
  • Prior and concurrent malignancies: There is an increasing number of patients with prior or concurrent malignancies or comorbidities. By excluding individuals with previous or concurrent cancers or comorbidities, older patients may be prevented from participating.

ASCO and Friends also worked with the National Cancer Institute (NCI) on revising its Generic Protocol Template (updated September 2018) to expand opportunities for participation in NCI-funded clinical trials by patients with certain health care conditions and or younger than age 18.

ASCO’s TAPUR™ Study includes broader patient eligibility criteria because the study involves only FDA-approved, targeted drugs. The TAPUR™ Study is a non-randomized clinical trial that aims to describe the safety and efficacy of targeted anticancer drugs that are prescribed for the treatment of patients who have both advanced cancer and a potentially actionable genomic alteration. To date, more than 2,000 patients have consented to participate, and nearly 1,450 have been treated with a TAPUR™ Study drug. View the list of eligibility requirements.

Read the letter.