Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

Conditions

• Advanced Malignant Solid Neoplasm
• Ann Arbor Stage III Non-Hodgkin Lymphoma
• Ann Arbor Stage IV Non-Hodgkin Lymphoma
• Histiocytic Sarcoma
• Juvenile Xanthogranuloma
• Langerhans Cell Histiocytosis
• Malignant Glioma
• Recurrent Childhood Rhabdomyosarcoma
• Recurrent Ependymoma
• Recurrent Ewing Sarcoma
• Recurrent Glioma
• Recurrent Hepatoblastoma
• Recurrent Langerhans Cell Histiocytosis
• Recurrent Malignant Germ Cell Tumor
• Recurrent Malignant Solid Neoplasm
• Recurrent Medulloblastoma
• Recurrent Neuroblastoma
• Recurrent Non-Hodgkin Lymphoma
• Recurrent Osteosarcoma
• Recurrent Peripheral Primitive Neuroectodermal Tumor
• Recurrent Primary Central Nervous System Neoplasm
• Recurrent Rhabdoid Tumor
• Recurrent Soft Tissue Sarcoma
• Refractory Ewing Sarcoma
• Refractory Glioma
• Refractory Hepatoblastoma
• Refractory Langerhans Cell Histiocytosis
• Refractory Malignant Germ Cell Tumor
• Refractory Malignant Solid Neoplasm
• Refractory Medulloblastoma
• Refractory Neuroblastoma
• Refractory Non-Hodgkin Lymphoma
• Refractory Osteosarcoma
• Refractory Peripheral Primitive Neuroectodermal Tumor
• Refractory Primary Central Nervous System Neoplasm
• Refractory Rhabdoid Tumor
• Refractory Rhabdomyosarcoma
• Rhabdoid Tumor
• Stage III Osteosarcoma AJCC v7
• Stage III Soft Tissue Sarcoma AJCC v7
• Stage IV Osteosarcoma AJCC v7
• Stage IV Soft Tissue Sarcoma AJCC v7
• Stage IVA Osteosarcoma AJCC v7
• Stage IVB Osteosarcoma AJCC v7
• Wilms Tumor

Eligibility Criteria

Sex

ALL

Age

12 Months - 21 Years

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Bone Marrow Aspiration and Biopsy — PROCEDURE
  Undergo a bone marrow and/or biopsy
• Bone Scan — PROCEDURE
  Undergo a bone scan
• Computed Tomography — PROCEDURE
  Undergo CT, PET/Ct, and/or CT/MRI
• Ensartinib — DRUG
  Given PO
• Erdafitinib — DRUG
  Given PO
• Ivosidenib — DRUG
  Given PO
• Laboratory Biomarker Analysis — OTHER
  Undergo molecular analysis
• Larotrectinib Sulfate — DRUG
  Given PO or via nasogastric- or gastric-tube
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI, PET/MRI, and/or CT/MRI
• Mutation Carrier Screening — PROCEDURE
  Undergo tumor tissue mutation screening
• Olaparib — DRUG
  Given PO
• Palbociclib — DRUG
  Given PO
• Pharmacological Study — OTHER
  Correlative studies
• Positron Emission Tomography — PROCEDURE
  Undergo PET, PET/CT, and/or PET/MRI
• Radionuclide Imaging — PROCEDURE
  Undergo radionuclide imaging
• Samotolisib — DRUG
  Given PO
• Selpercatinib — DRUG
  Given PO
• Selumetinib Sulfate — DRUG
  Given PO
• Tazemetostat — DRUG
  Given PO
• Tipifarnib — DRUG
  Given PO or via nasogastric or gastric tube
• Ulixertinib — DRUG
  Receive PO
• Vemurafenib — DRUG
  Given PO
• X-Ray Imaging — PROCEDURE
  Undergo an x-ray

Study Details

This phase II Pediatric MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.

Key Dates

Start date

Jul 31, 2017

Status verified

Jan 2026

Primary completion

Mar 31, 2025

Completion

Jan 6, 2027

Study Design

Enrollment

1,377 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SCREENING

Arms

• Experimental: Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion)
  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.
• Experimental: Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
  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.
• Experimental: Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene mutation)
  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.
• Experimental: Subprotocol D (TSC1, TSC2, or PI3K/mTOR gene mutation)
  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.
• Experimental: Subprotocol E (activating MAPK pathway gene mutation)
  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.
• Experimental: Subprotocol F (ALK or ROS1 gene alteration)
  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.
• Experimental: Subprotocol G (BRAF V600 gene mutation)
  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.
• Experimental: Subprotocol H (ATM, BRCA1, BRCA2, RAD51C, RAD51D mutations)
  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.
• Experimental: Subprotocol I (Rb positive, alterations in cell cycle genes)
  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.
• Experimental: Subprotocol J (MAPK pathway mutations)
  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.
• Experimental: Subprotocol K (IDH1 gene mutation)
  Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
• Experimental: Subprotocol M (HRAS gene alterations)
  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.
• Experimental: Subprotocol N (activating RET mutations)
  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.

Primary Outcome Measure

Proportion of Pediatric Patients Whose Advanced Tumors Have Pathway Alterations That Can be Targeted by Select Anti-cancer Drugs [ Time Frame: Up to 2 years from study entry ]

Locations (168)

Find similar trials in Birmingham, AL

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