The problem: Cancer drug trials age discriminate. Almost all cancer trials have a minimum age of eligibility at 18 years of age, with no scientific or ethical rationale. As a result, children and young teens are excluded from trials of new cancer drugs.
New cancer drugs are rarely studied in children before they are approved. The minimum age for participation in a clinical trial of a new cancer drug historically has been 18. Children are excluded from participating in adult trials even when a trial is conducted for a cancer that occurs in both adults and children.
While there are sometimes pediatric clinical trials of novel cancer therapies, these pediatric trials are conducted either years later, or never.
And, sometimes a pediatric trial is not scientifically preferable to inclusion of a child in an adult trial.
For most cancer drugs, there is no scientific rationale for the exclusion of children from trials.
When there are no kids in clinical trials, no data can be collected on how a drug works in kids. Most kids with cancer receive new drugs off-label – meaning the drug is being used in a manner not specified in the FDA’s approved packaging label, for instance, without dosing information.
The solution: Children should be included on all cancer trials unless there is a scientific or ethical rationale for their exclusion.
Kids v Cancer will be exploring and supporting a number of efforts to create a standard by which children, including very young children, are included on early clinical trials unless there is a scientific or ethical rationale not to.
Inclusion on adult cancer trials will give kids earlier access to most promising drugs.
Including children on adult cancer trials will create valuable information about which drugs should be further studied in children.
Moreover, inclusion of children on trials will, for certain trials, result in a robust data set regarding pediatric efficacy and toxicity.
Read an editorial by Nancy Goodman in the Cancer Letter, Too Many PD-1 Trials for Adults, Too Few for Children.
Support for including kids in trials
- FDA supports changing the minimum age for cancer drugs trials, inclusion of adolescents into adult oncology trials
FDA’s guidance “Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs” (June 2019) calls for early consideration of pediatric drug development and broadening eligibility criteria.
FDA’s draft guidance for industry “Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients” (March 2019) encourages including pediatric patients for conditions without known curative options in early-phase trials that assess dose, safety, and PK in a variety of tumor types when compelling nonclinical data and/or early adult clinical data suggest activity.
FDA’s final guidance “Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials” (March 2019) states that “Adolescent patients should be eligible for enrollment in adult oncology clinical trials at all stages of drug development when the histology and biologic behavior of the cancer under investigation is the same in, or the molecular target of the drug is relevant to, cancers in both adult and adolescent patients.”
The FDA encourages the early design and conduct of pediatric trials of investigational agents or the inclusion of pediatric patients in certain adult clinical trials when appropriate to expedite the development of safe and effective therapies to treat cancer in children.
“In order to facilitate earlier access to investigational and approved drugs for adolescent patients with cancer, and because drug exposure is most often similar in adolescents and adults, we recommend the inclusion of adolescents (ages 12-17) on disease and target-appropriate adult oncology trials.”
Read the full article, Enrolling adolescents in disease/target-appropriate adult oncology clinical trials of investigational agents, by Meredith K. Chuk, Yeruk Mulugeta, Michelle Roth-Cline, Nitin Mehrotra, Gregory H. Reaman.
“FDA will continue to support the expansion of patient eligibility criteria in oncology trials, thus improving generalizability and access to trials while ensuring patient safety.”
Read the full article in a Nature journal, Approvals in 2016: the march of the checkpoint inhibitors, by Gideon M. Blumenthal and Richard Pazdur.
- ASCO/FCR recommend including kids in adult cancer trials
American Society of Clinical Oncology and Friends of Cancer Research issued recommendations to lower the minimum age, which says: “We conclude that many of the historical concerns of including children early in oncology clinical trials do not apply in the current scientific and clinical environment of pediatric oncology and drug development. […] Including children in appropriately designed adult clinical oncology trials is feasible and can be done in a way that enhances their access to these agents without compromising safety or development strategies.”
Read the full article in the Journal of Clinical Oncology, Modernizing clinical trial eligibility: Recommendations of the ASCO–FCR Minimum Age Working Group.
- NIH support for including kids in cancer trials
Part of the recently enacted 21st Century Cures Act requires NIH Director Francis Collins to convene a workshop of experts on pediatric and older populations to provide input on “appropriate age groups to be included in research studies involving human subjects” and “acceptable justifications for excluding participants from a range of age groups from human subjects research studies.” Within six months after the workshop, NIH must determine whether it needs to update its policies on the inclusion of different age groups. This could change the way government-funded studies are conducted but will not affect industry-funded trials.
Read the text of the bill, Section 404N.
- ASCO’s TAPUR Study decreased enrollment age from 18 to 12
American Society of Clinical Oncology has been conducting a Targeted Agent and Profiling Utilization Registry (TAPUR) Study since March 2016, and currently enrolls 510 participants at 83 clinical sites in 20 states. Although not all therapies are available for patients <18, study leaders decreased the enrollment age from 18 to 12 years in 2017 to extend the opportunity for participation to adolescent patients with advanced cancer.
Read about Fostering Age Inclusive Research initiative in Europe to reduce minimum age for children.