Last month a teenage girl from Indiana became the first patient enrolled in an important early-phase NCI clinical trial at the NIH Clinical Center. Diagnosed with an aggressive form of a rare cancer, hereditary medullary thyroid carcinoma (MTC), this young woman will help determine whether the investigational agent vandetanib may be the first effective nonsurgical treatment in young patients with this cancer.

The trial is significant for another reason. It's the first being conducted at the NIH Clinical Center under the joint leadership of an NIH intramural clinical investigator and an extramural scientist. Dr. Frank Balis, from the Pediatric Oncology Branch in NCI's Center for Cancer Research (CCR), is the principal investigator (PI), while Dr. Samuel Wells, from Washington University in St. Louis and one of the world's foremost MTC experts, is the adjunct PI.

Dr. Wells was involved in the discovery of the proto-oncogene, called RET, associated with the hereditary disorder multiple endocrine neoplasia (MEN). Patients with subtypes of MEN are at high risk of developing MTC and other endocrine tumors. Dr. Wells also helped to establish the efficacy of prophylactic thyroidectomy in children with RET mutations associated with these MEN subtypes.

After leading early-phase trials that demonstrated the activity of vandetanib in adults with MTC, Dr. Wells approached NCI about conducting a trial in children. It offered an ideal opportunity to pursue something which NIH Clinical Center Director Dr. John Gallin has strongly advocated: an intramural/extramural scientist-led trial. NCI worked with NIH leaders to make the arrangements allowing Dr. Wells to serve as a PI of a Clinical Center trial.

It's gratifying that we were able to make this first-of-its-kind collaboration happen at the NIH Clinical Center, especially because it is with rare cancers that the Clinical Center's value truly shines.

For example, because NIH can recruit patients from around the country and provide them with financial and travel support, trials performed at the Clinical Center are more likely to enroll enough patients with rare diseases to provide the statistical power needed to produce meaningful results and inform clinical care.

Conducting the trial at the Clinical Center also allows investigators from three other NIH institutes with expertise in endocrinopathies and MEN syndromes to participate. In addition to helping to write the trial protocol, these investigators will provide clinical care to trial participants. And many patients in this trial - as well as members of their families, since this is a hereditary syndrome - will likely participate in additional studies, ensuring that we can achieve the most scientific value from and clinical benefit for each patient during their treatment.

The trial's phase I/II design allows it to both determine the safest drug dose that can be given to pediatric patients, and to evaluate its potential efficacy. The trial also will involve biomarker and pharmacokinetic analyses, as well as analyses of tumor samples in the laboratory of Dr. Paul Meltzer from the CCR Genetics Branch to study whether there are genetic mutations associated with resistance to the agent.

Taken as a whole, this trial highlights a new vision of collaboration and partnership. It maximizes the potential of a single trial to provide as much data as possible so that the results can be quickly translated into patient benefit.

Dr. John E. Niederhuber
Director, National Cancer Institute