This phase I trial studies the side effects and the best dose of WEE1 inhibitor AZD1775 when given together with local radiation therapy in treating children with newly diagnosed diffuse intrinsic pontine gliomas. WEE1 inhibitor AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. Giving WEE1 inhibitor AZD1775 with local radiation therapy may work better than local radiation therapy alone in treating diffuse intrinsic pontine gliomas.

Conditions: Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma Interventions:

Principal Investigator:
Josephine HaDuong, MD

Research Coordinator:
Kathryn Duvall
(714) 509-8646

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  • Clinical Trial Info
  • IRB Number: 130769
  • Sponsor: Children's Oncology Group
  • Protocol Number: ADVL1217
  • NCT Number: NCT01922076
  • Research Type: Adolescents and Young Adults, Brain Tumor/Central Nervous System/Neuro-Oncology, Recurrent/Refractory Cancer
  • Phase: I
  • Status: Active - Open to Enrollment

Key Inclusion Criteria:

  • Age:12 Months to 21 Years
  • Patients with recurrent or refractory solid tumors, including CNS tumors and lymphoma, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
  • Patients must have either measurable or evaluable disease
  • Standard COG Phase 1 organ function requirements.
  • Cardiac function: Shortening fraction of >= 27% by echocardiogram, or Ejection fraction of >= 50% by gated radionuclide study. No supraventricular arrhythmia on electrocardiogram (EKG). Prolonged rate corrected QT (QTc) interval < 500 msec.

Key Exclusion Criteria:

  • ​Patients with uncontrolled high blood pressure (i.e., systolic blood pressure > 99th percentile) are not eligible.
  • Patients with known cardiopulmonary disease are not eligible.
  • Patients with known hepatic cirrhosis or severe pre-existing hepatic impairment are not eligible.
  • Patients with uncontrolled coagulopathy or bleeding disorder are not eligible.
  • Patients must not have received enzyme-inducing anticonvulsants for at least 7 days prior to enrollment.
  • Patients who have received drugs that are strong or moderate inhibitors and/or inducers of CYP3A4 within 14 days prior to enrollment are not eligible; while on study, the following BCRP inhibitors (cyclosporine, eltrombopag, gefitinib) should be avoided if possible, and concomitant use of UGT1A1 inhibitors, such as diclofenac, ketoconazole, probenecid, silibinin, nilotinib and atazanavir, should be avoided because of potential for increased irinotecan toxicity.
    Patients with known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection are not eligible.