Purpose

This Pediatric MATCH screening and multi-sub-study phase II 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.

Category

IRB Number
20170690HU
NCT Number
NCT03155620
Open to Enrollment
Yes
Sponsor
National Cancer Institute (NCI) -



Study Contact

Principal Investigator
Anne-Marie Langevin

Jaclyn Hung
+1 (210) 450-5358
hungj@uthscsa.edu



Eligibility

Eligible Ages
Between 12 Months and 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    Exclusion Criteria


      Study Design

      Phase
      Phase 2
      Study Type
      Interventional
      Allocation
      Non-Randomized
      Intervention Model
      Parallel Assignment
      Primary Purpose
      Screening
      Masking
      None (Open Label)
      Condition
    1. Advanced Malignant Solid Neoplasm
    2. Ann Arbor Stage III Non-Hodgkin Lymphoma
    3. Ann Arbor Stage IV Non-Hodgkin Lymphoma
    4. Histiocytic Sarcoma
    5. Juvenile Xanthogranuloma
    6. Langerhans Cell Histiocytosis
    7. Malignant Glioma
    8. Recurrent Childhood Rhabdomyosarcoma
    9. Recurrent Ependymoma
    10. Recurrent Ewing Sarcoma
    11. Recurrent Glioma
    12. Recurrent Hepatoblastoma
    13. Recurrent Langerhans Cell Histiocytosis
    14. Recurrent Malignant Germ Cell Tumor
    15. Recurrent Malignant Solid Neoplasm
    16. Recurrent Medulloblastoma
    17. Recurrent Neuroblastoma
    18. Recurrent Non-Hodgkin Lymphoma
    19. Recurrent Osteosarcoma
    20. Recurrent Peripheral Primitive Neuroectodermal Tumor
    21. Recurrent Primary Central Nervous System Neoplasm
    22. Recurrent Rhabdoid Tumor
    23. Recurrent Soft Tissue Sarcoma
    24. Refractory Ewing Sarcoma
    25. Refractory Glioma
    26. Refractory Hepatoblastoma
    27. Refractory Langerhans Cell Histiocytosis
    28. Refractory Malignant Germ Cell Tumor
    29. Refractory Malignant Solid Neoplasm
    30. Refractory Medulloblastoma
    31. Refractory Neuroblastoma
    32. Refractory Non-Hodgkin Lymphoma
    33. Refractory Osteosarcoma
    34. Refractory Peripheral Primitive Neuroectodermal Tumor
    35. Refractory Primary Central Nervous System Neoplasm
    36. Refractory Rhabdoid Tumor
    37. Refractory Rhabdomyosarcoma
    38. Rhabdoid Tumor
    39. Stage III Osteosarcoma AJCC v7
    40. Stage III Soft Tissue Sarcoma AJCC v7
    41. Stage IV Osteosarcoma AJCC v7
    42. Stage IV Soft Tissue Sarcoma AJCC v7
    43. Stage IVA Osteosarcoma AJCC v7
    44. Stage IVB Osteosarcoma AJCC v7
    45. Wilms Tumor
    46. Arm Groups

      ArmDescriptionIntervention
      Experimental

      Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion)

      Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive Trk inhibitor LOXO-101 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.
    47. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    48. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    49. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    50. Procedure: Biospecimen Collection

      Undergo collection of blood

    51. Drug: Larotrectinib

      Given PO or via nasogastric- or gastric-tube

      Other names:

      • ARRY 470
      • LOXO 101
      • LOXO-101

    52. Other: Pharmacological Study

      Correlative studies

    53. 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.
    54. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    55. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    56. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    57. Procedure: Biospecimen Collection

      Undergo collection of blood

    58. Other: Pharmacological Study

      Correlative studies

    59. Drug: Tazemetostat

      Given PO

      Other names:

      • E7438
      • EPZ-6438
      • EPZ6438

    60. 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.
    61. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    62. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    63. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    64. Drug: Selumetinib Sulfate

      Given PO

      Other names:

      • AZD-6244 Hydrogen Sulfate
      • AZD6244 Hydrogen Sulfate
      • AZD6244 Hydrogen Sulphate
      • Koselugo
      • Selumetinib Sulphate

    65. Procedure: Biospecimen Collection

      Undergo collection of blood

    66. Other: Pharmacological Study

      Correlative studies

    67. 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.
    68. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    69. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    70. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    71. Drug: Vemurafenib

      Given PO

      Other names:

      • BRAF (V600E) kinase inhibitor RO5185426
      • BRAF(V600E) Kinase Inhibitor RO5185426
      • PLX-4032
      • PLX4032
      • RG 7204
      • RG7204
      • RO 5185426
      • Zelboraf

    72. Procedure: Biospecimen Collection

      Undergo collection of blood

    73. Other: Pharmacological Study

      Correlative studies

    74. 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.
    75. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    76. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    77. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    78. Drug: Palbociclib

      Given PO

      Other names:

      • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
      • Ibrance
      • PD 0332991
      • PD 332991
      • PD 991
      • PD-0332991

    79. Procedure: Biospecimen Collection

      Undergo collection of blood

    80. Other: Pharmacological Study

      Correlative studies

    81. 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.
    82. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    83. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    84. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    85. Procedure: Biospecimen Collection

      Undergo collection of blood

    86. Other: Pharmacological Study

      Correlative studies

    87. Drug: Selpercatinib

      Given PO

      Other names:

      • LOXO-292
      • RET Kinase Inhibitor LOXO-292
      • Retevmo
      • WHO 10967

    88. Experimental

      Subprotcol 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.
    89. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    90. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    91. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    92. Drug: Tipifarnib

      Given PO or via nasogastric or gastric tube

      Other names:

      • R115777
      • Zarnestra

    93. Procedure: Biospecimen Collection

      Undergo collection of blood

    94. Other: Pharmacological Study

      Correlative studies

    95. Experimental

      Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)

      Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive pan-FGFR tyrosine kinase inhibitor JNJ-42756493 PO once daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    96. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    97. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    98. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    99. Procedure: Biospecimen Collection

      Undergo collection of blood

    100. Drug: Erdafitinib

      Given PO

      Other names:

      • Balversa
      • JNJ-42756493

    101. Other: Pharmacological Study

      Correlative studies

    102. 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.
    103. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    104. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    105. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    106. Drug: Samotolisib

      Given PO

      Other names:

      • 2H-Imidazo(4,5-C)quinolin-2-one, 1,3-Dihydro-8-(5-(1-hydroxy-1-methylethyl)-3-pyridinyl)-1-((2S)-2-methoxypropyl)-3-methyl-
      • LY 3023414
      • LY-3023414
      • LY3023414
      • WHO 10889

    107. Procedure: Biospecimen Collection

      Undergo collection of blood

    108. Other: Pharmacological Study

      Correlative studies

    109. Experimental

      Subprotocol F (ALK or ROS1 gene alteration)

      Patients with an ALK or ROS1 gene alteration receive ensartinib (ALK Inhibitor X-396) PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
    110. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    111. Drug: Ensartinib

      Given PO

      Other names:

      • X-396

    112. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    113. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    114. Procedure: Biospecimen Collection

      Undergo collection of blood

    115. Other: Pharmacological Study

      Correlative studies

    116. 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.
    117. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    118. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    119. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    120. Procedure: Biospecimen Collection

      Undergo collection of blood

    121. Drug: Olaparib

      Given PO

      Other names:

      • AZD 2281
      • AZD-2281
      • AZD2281
      • KU-0059436
      • Lynparza
      • PARP Inhibitor AZD2281

    122. Other: Pharmacological Study

      Correlative studies

    123. 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.
    124. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    125. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    126. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    127. Procedure: Biospecimen Collection

      Undergo collection of blood

    128. Other: Pharmacological Study

      Correlative studies

    129. Drug: Ulixertinib

      Receive PO

      Other names:

      • BVD-523
      • VRT752271