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
20170689HU
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: Biospecimen Collection

      Undergo collection of blood

    48. Drug: Larotrectinib

      Given PO or via nasogastric- or gastric-tube

      Other names:

      • ARRY 470
      • LOXO 101
      • LOXO-101

    49. Other: Pharmacological Study

      Correlative studies

    50. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    51. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    52. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    55. Other: Pharmacological Study

      Correlative studies

    56. Drug: Tazemetostat

      Given PO

      Other names:

      • E7438
      • EPZ-6438
      • EPZ6438

    57. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    58. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    59. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    62. Other: Pharmacological Study

      Correlative studies

    63. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    64. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    65. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    66. Drug: Selumetinib Sulfate

      Given PO

      Other names:

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

    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: Biospecimen Collection

      Undergo collection of blood

    69. Other: Pharmacological Study

      Correlative studies

    70. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    71. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    72. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    73. 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

    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: Biospecimen Collection

      Undergo collection of blood

    76. Other: Pharmacological Study

      Correlative studies

    77. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    78. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    79. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    80. 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

    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: Biospecimen Collection

      Undergo collection of blood

    83. Other: Pharmacological Study

      Correlative studies

    84. Drug: Selpercatinib

      Given PO

      Other names:

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

    85. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    86. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    87. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    90. Other: Pharmacological Study

      Correlative studies

    91. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    92. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    93. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    94. Drug: Tipifarnib

      Given PO or via nasogastric or gastric tube

      Other names:

      • R115777
      • Zarnestra

    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: Biospecimen Collection

      Undergo collection of blood

    97. Drug: Erdafitinib

      Given PO

      Other names:

      • Balversa
      • JNJ-42756493

    98. Other: Pharmacological Study

      Correlative studies

    99. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    100. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    101. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    104. Other: Pharmacological Study

      Correlative studies

    105. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    106. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    107. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    108. 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

    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: Biospecimen Collection

      Undergo collection of blood

    111. Other: Pharmacological Study

      Correlative studies

    112. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    113. Drug: Ensartinib

      Given PO

      Other names:

      • X-396

    114. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    115. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    118. Drug: Olaparib

      Given PO

      Other names:

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

    119. Other: Pharmacological Study

      Correlative studies

    120. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    121. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    122. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening

    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: Biospecimen Collection

      Undergo collection of blood

    125. Other: Pharmacological Study

      Correlative studies

    126. Drug: Ulixertinib

      Receive PO

      Other names:

      • BVD-523
      • VRT752271

    127. Procedure: Biopsy

      Undergo biopsy

      Other names:

      • BIOPSY_TYPE
      • Bx

    128. Other: Laboratory Biomarker Analysis

      Undergo molecular analysis

    129. Procedure: Mutation Carrier Screening

      Undergo tumor tissue mutation screening