LOXO-TRK-15003: A Phase 1 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

Why are we doing this research?

PURPOSE:

This is a multicenter, open-label, Phase 1 study in pediatric patients with advanced solid or primary CNS tumors. LOXO101 will be administered orally (PO) twice daily (BID), with the dose adjusted by body surface area (BSA).

DETAILED DESCRIPTION:

  • This is a multicenter, open-label, Phase 1 study in pediatric patients with advanced solid or primary CNS tumors. LOXO101 will be administered orally (PO) twice daily (BID), with the dose adjusted by body surface area (BSA).
  • Dose Escalation Phase Escalation will proceed through the planned 4 dose levels, or until the MTD is reached, or until the Sponsor determines that a suitable dose has been achieved based on PK exposure.
  • Expansion Cohorts Additional patient cohorts may be enrolled to better characterize safety and efficacy in patients with specific abnormalities in the NTRK genes or proteins.

Study Type: Interventional

Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 1 Month to 21 Years

ELIGIBILITY CRITERIA

Inclusion Criteria:

  • Pediatric patients ≥ 1 year old on Cycle 1 Day 1 (C1D1)
  • Locally advanced or metastatic solid or primary CNS tumor that has progressed, or was nonresponsive to available therapies, and for which no standard or available curative therapy exists
  • Or patients ≥ 1 month old with a diagnosis of infantile/congenital fibrosarcoma, with a documented NTRK fusion that has progressed, or was nonresponsive to available therapies and for which no standard or available curative therapy exists
  • Karnofsky (those 16 years old or older) or Lansky (those younger than 16 years) performance score of at least 50
  • Adequate hematologic function: Absolute neutrophil count (ANC) ≥ 1.0 109/L, platelet count ≥ 100.0 109/L and hemoglobin ≥ 8.0 g/dL (patients with bone marrow involvement will not be evaluable for hematologic DLT and can enroll with ANC ≥ 0.75 109/L, platelet count ≥ 75.0 109/L and hemoglobin ≥ 8.0 g/dL)
  • Adequate hepatic function: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 upper limit of normal (ULN) for age (patients with documented Gilbert's Disease may be enrolled with Sponsor approval) and SGPT (ALT) ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
  • Adequate renal function: Estimated glomerular filtration rate ≥ 30 mL/minute using the Cockroft-Gault formula or: a serum creatinine based on age/gender as outlined in the protocol
Exclusion Criteria:
  • Investigational agent, anticancer therapy, or major surgery within 28 days (4 weeks) prior to C1D1
  • Symptomatic brain metastases, leptomeningeal carcinomatosis, or spinal cord compression
  • Clinically significant active cardiovascular disease or history of prolonged QT interval corrected for heart rate (QTc)
  • Current treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer (EIAEDs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed)

Conditions

  • Brain Spinal Tumors Medulloblastoma Relapse
  • Brain Spinal Tumor Low Grade Glioma Relapse
  • Brain Spinal Tumor DIPG Relapse
  • Brain and Spinal Tumor Ependymoma Relapse
  • Brain Spinal Other ATRT
  • Brain Spinal Other Craniopharyngioma
  • Brain Spinal Other Germ Cell Tumor
  • Brain Spinal Other Choroid Plexus Tumor
  • Brain Spinal Other All Other
  • Brain Spinal Neurofibromatosis OPG
  • Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Sarcoma Ewing Relapse
  • Sarcoma Osteosarcoma Relapse
  • Sarcoma Rhabdomyosarcoma Relapse
  • Neuroblastoma Relapse - Refractory
  • Liver Relapse - Refractory
  • Kidney Relapse - Refractory
  • Solid Tumor Retinoblastoma Relapse - Refractory
  • Solid Tumor Neurofibromatosis OPG Low Grade Glioma
  • Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Solid Tumor Melanoma Relapse - Refractory
  • Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Solid Tumors - All Other
  • Adult - Brain Spinal Tumors Medulloblastoma Relapse
  • Adult - Brain Spinal Tumor Low Grade Glioma Relapse
  • Adult - Brain Spinal Tumor DIPG Relapse
  • Adult - Brain and Spinal Tumor Ependymoma Relapse
  • Adult - Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Adult - Brain Spinal Other All Other
  • Adult - Brain Spinal Neurofibromatosis OPG
  • Adult - Brain Spinal Other ATRT
  • Adult - Brain Spinal Other Choroid Plexus Tumor
  • Adult - Brain Spinal Other Craniopharyngioma
  • Adult - Brain Spinal Other Germ Cell Tumor
  • Adult - Sarcoma Ewing Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Rhabdomyosarcoma Relapse
  • Adult - Neuroblastoma Relapse - Refractory
  • Adult - Liver Relapse - Refractory
  • Adult - Kidney Relapse - Refractory
  • Adult - Solid Tumor Retinoblastoma Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis OPG Low Grade Glioma
  • Adult - Solid Tumor Melanoma Relapse - Refractory
  • Adult - Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Adult - Solid Tumors - All Other

Contact

For more information contact:
Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org