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

Titre officiel

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

Sommaire:

Cette étude vise à évaluer l’administration du palbociclib en association avec la chimiothérapie (témozolomide avec irinotécan et/ou topotécan avec cyclophosphamide) aux enfants, aux adolescents et aux jeunes adultes présentant une tumeur solide récidivante ou réfractaire. L’objectif principal de la phase I de cette étude est d’évaluer l’innocuité du palbociclib en association avec la chimiothérapie afin d’estimer la dose maximale tolérée. L’objectif principal de la phase II est de comparer l’efficacité du palbociclib en association avec l’irinotécan et le témozolomide par rapport à l’irinotécan et au témozolomide en monothérapie dans le traitement des enfants, des adolescents et des jeunes adultes atteints du sarcome d’Ewing (EWS) récidivant ou réfractaire. Les paramètres pharmacocinétiques et l’efficacité du palbociclib en association avec la chimiothérapie seront évalués.

Description de l'essai

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)

Voir cet essai sur ClinicalTrials.gov