By Rose Pagano and Suzanne M. Sensabaugh, MS, MBA


Pediatric cancer is frequently different than cancer found in adults and requires unique treatments. Conversely, certain cancers (soft tissue and bone sarcomas, central nervous system tumors, leukemias and lymphomas, and melanoma) in adolescents are similar to those found in adults.  Typically, age restrictions disqualify adolescents from participation in adult oncology trials. Also, drug trials for adolescents usually beginning after the drug is approved for adults. As a result, adolescent patients may have delayed access to potentially beneficial drugs.

The FDA recently released “Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials Guidance for Industry” to convey information regarding the incorporation of adolescent patients (ages 12 to 17) in adult oncology clinical trials to the pharmaceutical industry and clinical investigators. According to the document, the FDA recommends involving adolescents in the appropriate adult oncology trials to facilitate more preemptive examination and approval of drugs for adolescents with cancer. The guidance details ethical requirements, safety procedures, dosing and pharmacokinetic (PK) evaluations, and necessary conditions for the incorporation of adolescent patients in adult oncology trials in the numerous stages of drug development.

This guidance is intended to be a general overview for sponsors debating the use of this approach. Obviously, the specific elements of a drug development program in adult oncology that incorporates adolescent patients differs based on the drug and disease being analyzed. Due to this variability, it is recommended that sponsors contact the necessary FDA review division to discuss details before the program is initiated with patients.

Generally, the document states that adult oncology clinical trials at any stage in drug development should be accessible to adolescent patients when the histology and biologic behavior of the cancer being tested is the same in both patient groups. For both first-in-human and dose-escalation trials, adolescents can be involved with the trial once the initial adult PK and toxicity data has been collected. Sponsors should contact the FDA review division to decide if the data is sufficient enough to enroll adolescents.

If the adolescent patients are going to be early dose cohorts, the doses should satisfy 21 CFR 50.52 Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects. Usually, adolescents involved in early phase trials should have cancers that have relapsed or are refractory to typical therapies. In activity estimating or confirmatory trials, adolescents are allowed to be admitted to the program concurrently with adults.

Additionally, the necessary drug doses for adolescents should be determined based on if the adult dosage is according to body size or fixed dose. For drugs that are given in a fixed dose, there should be a minimum body weight adolescents need to meet to receive the drug. Based on research conducted by the FDA, 40 kg is usually the safest minimum body weight.

For these clinical trials, a suggested dosage needs to be reinforced by PK characteristics of the drug in question. It is important to keep in mind how the adolescent patient’s size will influence the drug’s pharmacokinetics, therapeutic index of drug, and dose and exposure response relationships. PK analysis for adolescents should be conducted when adolescents become involved in the drug development program.

Safety monitoring was also mentioned in the document. Information gathered during the course of the trial concerning safety should be analyzed for age-related differences. Developmental toxicities, such as growth derangements and fertility issues, resulting from drug exposure should be analyzed in a longitudinal evaluation. Juvenile animal studies are not always required before including adolescents in oncology clinical trials unless data do not provide sufficient information on toxicity.

All in all, enrolling adolescents in relevant adult oncology trials with the necessary dose considerations and safety monitoring is justified by the life-threatening nature of their disease.


At HartmannWillner LLC we understand the regulatory requirements for FDA approval, such as the requirements explained above for oncology studies. With our help, you can develop a realistic strategy that will move your product closer to approval as you reach each regulatory milestone.  Contact us today to learn more about our services and how we can help you.




Nitisha Pyndiah - Biotech Consulting Services

Suzanne M. Sensabaugh has advanced the development of over 130 biologics, biosimilars, and combination products since 2009. She can be reached at