Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumours

Official Title

PHASE 1/2 STUDY TO EVALUATE PALBOCICLIB (IBRANCE(REGISTERED)) IN COMBINATION WITH IRINOTECAN AND TEMOZOLOMIDE AND/OR IN COMBINATION WITH TOPOTECAN AND CYCLOPHOSPHAMIDE IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS

Summary:

This study will evaluate palbociclib in combination with chemotherapy (temozolomide with irinotecan and/or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumours. The main purpose of phase 1 portion of this study is to evaluate the safety of palbociclib in combination with chemotherapy in order to estimate the maximum tolerated dose. The main purpose of phase 2 portion is to compare the efficacy of palbociclib in combination with irinotecan and temozolomide vs irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS). Pharmacokinetics and efficacy of palbociclib in combination with chemotherapy will be evaluated.

Trial Description

Primary Outcome:

• Phase 2 open-label, randomized: Event-free survival (EFS) in irinotecan and temozolomide with palbociclib treatment arm will be compared to EFS in treatment with irinotecan and temozolomide alone treatment arm..
• Phase 1: Dose Escalation Part and Dose Determination Part: Frequency of dose-limiting toxicities (DLT)
• Phase 1: Dose Expansion Parts: Frequency of adverse events
• Phase 1: Dose Expansion Parts: Percentage of Participants With Complete Response or Partial Response

• Phase 1 and Phase 2: Frequency of adverse events
• Phase 1 and Phase 2: Percentage of participants with laboratory abnormalities
• Phase 1 and Phase 2: Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
• Phase 1 and Phase 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
• Phase 1 and Phase 2: Percentage of Participants With Complete Response or Partial Response
• Phase 1 and Phase 2: Duration of response (DoR) for Participants Who Achieved Complete Response or Partial Response
• Phase 1 and Phase 2: Progression Free Survival (PFS)
• Phase 1 and Phase 2: Overall Survival (OS)
• Phase 2 : comparison of PET-CT response assessment to objective response on CT/MRI.
• Phase 2: the impact of the combination of palbociclib with TMZ and IRN treatment on the quality of life (QoL) of patients with refractory or recurrent EWS.
• Phase 1 and Phase 2:Palbociclib Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
• Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Maximum plasma concentration time (Tmax)
• Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
• Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
• Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Oral plasma clearance (CL/F)
• Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
• Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum plasma concentration time (Tmax)
• Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
• Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
• Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Oral plasma clearance (CL/F)
• Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
• Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)
• Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
• Phase 1 and Phase 2: Irinotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
• Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)
• Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)
• Phase 1: Topotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
• Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
• Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)
• Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
• Phase 1: Cyclophosphamide Pharmacokinetics, Oral plasma clearance (CL/F)
• Phase 1: Cyclophosphamide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
• Phase 1: Cyclophosphamide Pharmacokinetics, Maximum plasma concentration time (Tmax)
• Phase 1: Cyclophosphamide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
• Phase 1: Cyclophosphamide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)

View this trial on ClinicalTrials.gov