ADV1414: Phase I Study of Selinexor to Treat Patients with Recurrent and Refractory Pediatric Solid Tumors

Brief Summary

This study will test the effects of selinexor (KPT-330) on children between the ages of 1 and 21 who have recurrent and refractory solid tumors, including lymphoma and CNS tumors. Children with these kinds of aggressive tumors have few treatment options and have a high rate of mortality. Selinexor is an experimental drug that has shown some promise in the lab as a treatment for acute myeloid leukemia, sarcoma, and other solid tumors. It has been administered to adults in Phase 1 trials with no severe, unmanageable side effects. This study will determine how much selinexor may be safely given to children who have recurrent and refractory brain and solid tumors. The trial will also examine selinexor’s impact on the rest of the body and its effects on tumor tissue of patients with recurrent or refractory high grade gliomas (HGG).

Primary Objectives

• To determine the recommended phase 2 dose or the maximum tolerated dose of the tablet form of selinexor in children with recurrent or refractory solid and CNS tumors
• To describe the toxic effects of selinexor 
• To characterize the pharmacokinetics of the tablet form of selinexor

Eligibility Criteria

Inclusion criteria include:

• At least 1 but not more than 21 years old
• Able to swallow tablets whole
• Diagnosed with one of the following:
  • Recurrent or refractory solid tumor, including lymphoma and CNS tumors
  • Intrinsic brain stem tumor, optic pathway glioma, or a pineal tumor and elevations of CSF or serum tumor markers
  • Recurrent or refractory high grade glioma, including disseminated tumors (excluding DIPG), not requiring surgical resection
  • Recurrent or refractory HGG requiring surgical resection (excluding DIPG and disseminated tumors) and is medical stable to receive 3-4 doses of selinexor before undergoing surgery

Exclusion criteria include: 

• Pregnant or breast-feeding
• Receiving corticosteroids and has not been on a stable or decreasing dose for at least 7 days prior to enrollment
• Currently taking another investigational drug
• Currently receiving other anti-cancer agents
• Has had a solid organ transplant
• BMI less than 3rd percentile for age
• Macular degeneration, uncontrolled glaucoma or cataracts
• Body surface area less than 0.84m²

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

Collaborating sites in the U.S.

About this Clinical Trial

There are very few, effective treatments for aggressive pediatric brain and solid tumors. These tumors include those that come back after treatment, also known as recurrent, and tumors that don’t respond to therapy, also known as refractive. 

Researchers have tested new, experimental drugs to find a treatment that may fight these kinds of tumors better. One of those drugs is called selinexor, also known as KPT-330. Selinexor has shown promise in fighting cancer in test tubes and animals. It has also been used in adults with no severe side effects, but doctors don’t yet know if younger patients will respond in the same way. St. Jude is offering this Phase I study to see how selinexor can benefit children, adolescents and young adults with these kinds of tumors.

Purpose of this clinical trial

The main goal of this study is to find out how much selinexor may be given safely to children who have these kinds of aggressive tumors without causing severe side effects. Researchers also want to find out how well selinexor treats these tumors and want to learn more about the drug’s effects on the rest of the body.

Eligibility Overview

• Diagnosis of solid tumor that did not respond to treatment or came back after treatment, including lymphoma and central nervous system tumors
• At least 1 but not more than 21 years of age
• Able to swallow tablets whole