Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumours And/Or Who Have No Satisfactory Treatment Options

Official Title

A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumours And/Or Who Have No Satisfactory Treatment Options

Summary:

This is an open-label, Phase 1/2 multicentre dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumours (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumours harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumours harboring NTRK1/2/3 or ROS1 gene fusions.

Trial Description

Primary Outcome:

• Maximum Tolerated Dose (MTD)
• Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules
• Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules
• Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube)
• Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules
• Objective Response Rate (ORR)

• Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03
• Maximum observed plasma drug concentration (Cmax) using F1 Formulation
• Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact
• Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube
• Maximum observed plasma drug concentration (Cmax) using minitablets/F15
• Time to Cmax, by inspection (Tmax) using F1 Formulation
• Time to Cmax, by inspection (Tmax) using F06 Formulation given intact
• Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube
• Time to Cmax, by inspection (Tmax) using minitablets/F15
• AUC at steady state (AUCss) using F1 Formulation
• AUC at steady state (AUCss) using F06 Formulation given intact
• AUC at steady state (AUCss) using F06 Formulation administered via feeding tube
• AUC at steady state (AUCss) using minitablets/F15
• Terminal half life (t½) using F1 Formulation
• Terminal half life (t½) using F06 Formulation given intact
• Terminal half life (t½) using F06 Formulation administered via feeding tube
• Terminal half life (t½) using minitablets/F15
• Area under the drug concentration by time curve (AUC) using F1 Formulation
• Area under the drug concentration by time curve (AUC) using F06 Formulation given intact
• Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube
• Area under the drug concentration by time curve (AUC) using minitablets/F15
• Progression-free Survival (PFS)
• Overall Survival (OS)
• Duration of Response (DOR)
• Time to response (TTR)
• Clinical Benefit Rate (CBR)

View this trial on ClinicalTrials.gov