STARTRK: Phase I/II Study of Entrectinib in Children and Young Adults with Aggressive Solid or Brain Tumors (CLOSED TO ACCRUAL)

Brief Summary

This is a Phase I/II multicenter, open-label dose escalation study of entrectinib in pediatric and young adult patients with relapsed or refractory extracranial solid tumors, with additional expansion cohorts in patients with primary brain tumors harboring NTRK1/2/3, ROS1 or ALK molecular alterations and extracranial solid tumors harboring NTRK1/2/3, ROS1 or ALK gene fusions.

Entrectinib (also known as RXDX-101) is a potent inhibitor of the tyrosine kinases TRKA, TRKB, TRKC, ROS1 and ALK. In vivo, entrectinib demonstrates tumor eradication and tumor growth inhibition in multiple xenograft models of target-expressing tumors. Entrectinib also crosses the blood-brain barrier, enabling potential targeting of central nervous system disease.

All patients in this study will receive entrectinib administered orally, once daily, in repeated 4-week (28-day) cycles on an outpatient basis.

Primary Objective

• To determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D) and objective response rate of entrectinib.

Eligibility Criteria

Inclusion criteria include:

• Diagnosed with one of the following:
  • Relapsed or refractory extracranial solid tumor
  • Primary brain tumor with NTRK1/2/3, ROS1 or ALK gene fusion
  • Extracranial solid tumor with NTRK1/2/3, ROS1 or ALK gene fusion
• Younger than 22 years old
• Must have relapsed after or failed to respond to frontline, curative therapy OR no other potentially curative treatment options available (for patients undergoing first-line treatment)
• Adequate bone marrow function
• Not pregnant

Exclusion Criteria include:

• Currently participating in another clinical trial
• Known congenital long QT syndrome
• Known active infections
• Prior treatment with approved or investigational TRK, ROS1 or ALK inhibitors (Phase II)
• Active gastrointestinal disease

Study Design

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

Collaborating sites in the U.S.

About this study

This clinical trial will study the investigational drug entrectinib in children and adolescents with solid tumors and brain tumors. Investigational means that the drug has not been approved by health authorities. Entrectinib has been tested in adults. However, this study is the first time this drug is being tested in children.

Entrectinib is designed to target certain changes in cancer cells which may result in killing those cells.

This study is divided into two parts:

• The first part will test different doses of entrectinib to find out the highest dose that can be given without serious side effects.
• The second part will test entrectinib in patients who have specific changes in their cancer cells that may respond to the drug.

Because there is not much information about how entrectinib will affect cancers in humans, we do not know if you will benefit from taking part in this study. However, the information learned from this study may help doctors learn more about entrectinib as a treatment for these kinds of tumors. This information could help future participants with cancer.

Purpose of this clinical trial

The main goals of this study are:

• To test the safety, tolerability and anti-tumor activity of entrectinib
• To find out the highest dose of entrectinib that can be given without serious side effects
• To find out how your body handles and breaks down entrectinib
• To find out how entrectinib may benefit you or alter your cancer

Eligibility overview

• Diagnosed with one of the following:
  • Relapsed or refractory extracranial solid tumor
  • Primary brain tumor with NTRK1/2/3, ROS1 or ALK gene fusion
  • Extracranial solid tumor with NTRK1/2/3, ROS1 or ALK gene fusion
• Younger than 22 years old
• Not pregnant