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Kinase Inhibitor

Genetic Testing-Directed Therapy for Pediatric Cancer

Phase 2

Recruiting

Led By Donald W Parsons

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Bilirubin =< 1.5 x upper limit of normal (ULN) for age

Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses, and central nervous system (CNS) tumors are eligible

Must not have

Patients who have an uncontrolled infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying how well treatment that is directed by genetic testing works in pediatric patients with solid tumors or non-Hodgkin lymphomas.

Who is the study for?

This trial is for pediatric patients aged 12 months to 21 years with advanced solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have worsened after treatment or lack standard survival-prolonging treatments. They must have recovered from previous therapies' side effects, be able to swallow pills, and meet specific blood count and organ function criteria.

What is being tested?

The Pediatric MATCH trial tests if targeted therapy based on genetic testing can effectively treat children's cancers. It involves various interventions like imaging scans and biopsies to identify mutations in tumor genes, followed by matching patients with medications targeting those mutations.

What are the potential side effects?

Potential side effects depend on the specific medication given but may include fatigue, nausea, liver issues (elevated enzymes), skin reactions (rash), digestive problems (diarrhea), blood cell changes leading to increased infection risk or bleeding tendencies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My bilirubin levels are within the normal range for my age.

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I have a recurring or hard-to-treat tumor, including in the brain, lymph system, or other solid tumors.

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I am mostly able to care for myself and carry out daily activities.

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My kidney function, measured by creatinine clearance or GFR, is normal or above.

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I am between 12 and 21 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any infections that are currently uncontrolled.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (complete response/partial response)

Proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs

Secondary study objectives

Incidence of research biopsy related target toxicity

Percentage of patients with grade 3 or 4 adverse events

Pharmacokinetic (PK) parameters

+1 more

Other study objectives

Change in genomics in advanced pediatric cancers

Diagnostic and profiling genomics of tumor approach

Frequency of germline cancer susceptibility mutations in children with relapsed solid tumors and non-Hodgkin lymphomas

+2 more

Side effects data

From 2021 Phase 1 & 2 trial • 24 Patients • NCT03010358

33%

Infusion Related Reaction

33%

Alanine aminotransferase increased

33%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

17%

Sinusitis

17%

Tumor Lysis Syndrome

17%

Interoperative Hemorrhage

17%

Platelet count decreased

17%

Febrile neutropenia

17%

Infusion related reaction

17%

Upper respiratory infection

17%

Otitis externa

100%

80%

60%

40%

20%

Study treatment Arm

Phase 1, Dose 1 (400 mg Entospletinib Daily)

Phase 2 and MTD (800 mg Entospletinib Daily)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Subprotocol N (activating RET mutations)Experimental Treatment11 Interventions

Patients with activating RET gene alterations receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.

Group II: Subprotocol J (MAPK pathway mutations)Experimental Treatment6 Interventions

Patients with MAPK pathway mutations receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Group III: Subprotocol I (Rb positive, alterations in cell cycle genes)Experimental Treatment6 Interventions

Patients with Rb positive advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations in cell cycle genes receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Group IV: Subprotocol H (ATM, BRCA1, BRCA2, RAD51C, RAD51D mutations)Experimental Treatment6 Interventions

Patients deleterious ATM, BRCA1, BRCA2, RAD51C, or RAD51D gene mutations receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group V: Subprotocol G (BRAF V600 gene mutation)Experimental Treatment6 Interventions

Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group VI: Subprotocol F (ALK or ROS1 gene alteration)Experimental Treatment13 Interventions

Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.

Group VII: Subprotocol E (activating MAPK pathway gene mutation)Experimental Treatment6 Interventions

Patients with an activating MAPK pathway gene mutation receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group VIII: Subprotocol D (TSC1, TSC2, or PI3K/mTOR gene mutation)Experimental Treatment6 Interventions

Patients with a TSC1, TSC2, or PI3K/mTOR gene mutations receive PI3K/mTOR inhibitor LY3023414 PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group IX: Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene mutation)Experimental Treatment6 Interventions

Patients with an EZH2, SMARCB1, or SMARCA4 gene mutation receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group X: Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)Experimental Treatment12 Interventions

Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.

Group XI: Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion)Experimental Treatment6 Interventions

Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib sulfate PO or via nasogastric- or gastric-tube BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Group XII: Subprotcol M (HRAS gene alterations)Experimental Treatment6 Interventions

Patients receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Positron Emission Tomography

2011

Completed Phase 2

~2200

Bone Marrow Aspiration and Biopsy

2016

Completed Phase 1

~40