Pediatric Phase I Clinical Trial
Phase I clinical trial of p28 in pediatric patients with Recurrent or Progressive CNS tumors
We recently completed a national, multi-center trial (9 institutions) Phase I a, b clinical trial of p28 (NSC7451040) in pediatric patients with recurrent or progressive CNS tumors supported by the Pediatric Brain Tumor Consortium (PBTC-041) and NCI-DCT-CTEP.
Pediatric patients were administered p28 i.v. 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (50 mg/kg/course) using a rolling 6 study design. Serum pharmacokinetics were established. A total of 18 patients were registered on the study, 12 patients with malignant glioma, choroid plexus carcinoma, medulloblastoma, pineoblastoma, DIPG and AT/RT completed the DLT period and were evaluable for toxicity.
Seven patients received ≥2 courses and the most common adverse event attributed to p28 was a transient Grade I infusional reaction. One patient with metastatic pineoblastoma with bone marrow involvement had 2 DLTs of Grade 4 neutropenia and thrombocytopenia unrelated to drug administration. p28 was well tolerated in patients with recurrent or progressive CNS tumors. Pharmacokinetic analysis revealed an overall t½ and t½α similar to those of adults. An increased AUC was observed in pediatric patients, as a result of a higher Cmax and longer t½αβ.
p28 is well tolerated in children with recurrent or progressive CNS malignancies at the adult MTD. Patient risk appears minimal as p28 is not immunogenic with negligible adverse side effects nor clinical toxicity. These suggest that the clinical implications for p28 as a single agent or in combination with other chemotherapeutic agents are potentially significant.