ADVL1921, Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Palbociclib (Ibrance®) in Combination with Irinotecan and Temozolomide in Pediatric Patients with Recurrent or Refractory Solid Tumors (A5481092)

This is a Phase 1, open-label, multicenter, single-arm, rolling 6 dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic (PD) study of palbociclib in combination with chemotherapy backbone, temozolomide (TMZ) and irinotecan (iRn), in sequential cohorts of pediatric patients with recurrent/refractory solid tumor for whom no standard therapy is available. The study will be comprised of 3 parts: dose escalation part followed by a dose expansion cohort, and if applicable, followed by tumor-specific cohorts. in the dose escalation part, palbociclib will be administered orally QD (one a day) on Days 1-14, with doses of TMZ administered daily (intravenous (iV)/orally) on Days 1-5 and iRn administered daily iV on Days 1-5. Dose escalation or de-escalation will proceed according to decision rules outlined in Table 4 of the protocol following a rolling 6 design. For patients who cannot swallow TMZ capsules, TMZ will be administered as an iV infusion. TMZ can be given at the same time as palbociclib and will be administered at least 1 hour prior to administering iRn due to the fact that preclinical data suggests schedule-dependent effects. Patients who are unable to swallow the capsules should receive an iV formulation of TMZ, administered according to the product information, and can be given at the same time as palbociclib. iRn infusion will then be given at least 1 hour after completion of TMZ infusion.