RECRUITING

A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

Conditions

High Grade Glioma Diffuse Intrinsic Pontine Glioma NTRK gene fusion BABYPOG HIT-SKK Larotrectinib

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given. The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.

Official Title

A Pilot and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion

Quick Facts

Study Start:2021-04-08

Study Completion:2025-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04655404

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible. * Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site. * Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis. * Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort. * Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria) * Organ Function Requirements: Adequate Bone Marrow Function Defined as:	* Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Concomitant Medications Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible. * Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection. * Patients who have received prior solid organ transplantation are not eligible. * Patients must not have malabsorption syndrome or other condition affecting oral absorption. * Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study. * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Inclusion Criteria

Exclusion Criteria

* Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
* Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.
* Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.
* Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.
* Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)
* Organ Function Requirements: Adequate Bone Marrow Function Defined as:

* Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
* Concomitant Medications Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.
* Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
* Patients who have received prior solid organ transplantation are not eligible.
* Patients must not have malabsorption syndrome or other condition affecting oral absorption.
* Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Contacts and Locations

Study Contact

Amy K Jones, MSN

CONTACT

16147223284

connect@nationwidechildrens.org

Principal Investigator

Susan Chi, MD

STUDY_CHAIR

Dana Farber/ Boston Children's Cancer and Blood Disorders Center

Maryam Fouladi, MD

STUDY_CHAIR

Nationwide Children's Hospital

Study Locations (Sites)

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Children's National Medical Center

Washington, District of Columbia, 20010

United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Duke University Health System

Durham, North Carolina, 27708

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Nationwide Children's Hospital

Columbus, Ohio, 43235

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Texas Children's Hospital

Houston, Texas, 77030

United States

Seattle Children's Hospital

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: Nationwide Children's Hospital

Susan Chi, MD, STUDY_CHAIR, Dana Farber/ Boston Children's Cancer and Blood Disorders Center
Maryam Fouladi, MD, STUDY_CHAIR, Nationwide Children's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-08

Study Completion Date2025-12-01

Study Record Updates

Study Start Date2021-04-08

Study Completion Date2025-12-01

Terms related to this study

Keywords Provided by Researchers

NTRK gene fusion
BABYPOG
HIT-SKK
Larotrectinib

Additional Relevant MeSH Terms

High Grade Glioma
Diffuse Intrinsic Pontine Glioma