Name of the Trial
Phase I Study of Talabostat in Combination with Temozolomide or Carboplatin in Pediatric Patients with Relapsed or Refractory Solid Tumors, Including Brain Tumors (NCI-05-C-0239). See the protocol summary at http://cancer.gov/clinicaltrials/NCI-05-C-0239.

Principal Investigator
Dr. Frank M. Balis, NCI CCR

Why This Trial Is Important
Children and adolescents with solid tumors that are resistant to standard chemotherapy or have recurred after treatment have a relatively poor prognosis because of the lack of alternative therapies.

However, new-generation targeted agents now in clinical trials can increase the effectiveness of conventional chemotherapy drugs. One such agent is talabostat, a drug first developed to enhance the recovery of normal blood cells after chemotherapy. In cancer models in animals, talabostat also induces the immune system to mount an antitumor response capable of shrinking tumors or slowing their growth, and augments tumor response to standard chemotherapy drugs.

How talabostat triggers an antitumor immune response is not completely understood, but it is known that the drug blocks an enzyme, fibroblast activation protein (FAP), produced by tumor-associated fibroblasts (cells present in the connective tissue, or stroma, surrounding solid tumors). Inhibition of FAP increases production of a variety of cytokines that boost the activity of immune-system cells.

This trial assesses the safety of talabostat in combination with chemotherapy in pediatric patients with cancer. Depending on tumor type and prior treatment, trial participants will receive temozolomide or carboplatin, both standard chemotherapy agents, followed by talabostat. Talabostat will be given by mouth once daily in gradually increasing doses in small subgroups of patients until the optimal dose is determined. Blockage of a blood-borne enzyme closely related to FAP will also be measured during treatment and will serve as an indicator of talabostat's effectiveness.

Who Can Join This Trial
Researchers will enroll 24 patients between the ages of 2 and 19 with solid tumors that have not responded to, or have recurred after, standard chemotherapy. See the list of eligibility criteria at http://www.cancer.gov/clinicaltrials/NCI-05-C-0239.

Study Site and Contact Information
The trial is taking place at the NIH Clinical Center in Bethesda, Md. For more information, contact the NCI Clinical Studies Support Center at 1-888-NCI-1937. The toll-free call is confidential.