This phase I clinical trial studies the side effects and best dose of AZD1390 and to see how well it works when given together with radiation therapy for the treatment of pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma. AZD1390 is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to repair deoxyribonucleic acid damage caused by cancer treatments, such as radiation therapy. This may help overcome resistance to therapy seen in these cancers and therefore lead to increased death of cancer cells. Radiation therapy uses high energy x-rays or particles to kill cancer cells and shrink tumors. Giving AZD1390 with radiation may be safe, tolerable, and effective in treating pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma.
COHORT A and COHORT B: For the dose escalation phase, patients must be ≥ 12 months and < 18 years of age at the time of study enrollment
COHORT C and COHORT D: For the disease expansion phase, patients must be ≥ 12 months and < 22 years of age at the time of study enrollment
Patients with newly diagnosed primary high-grade glioma (HGG), diffuse midline glioma (DMG) (excluding primary spinal tumors), or diffuse intrinsic pontine glioma (DIPG) who are eligible to receive 54-59.4 Gray (Gy) fractionated radiation at 1.8 Gy/day. Patients must have had histologic verification of malignancy at original diagnosis except in patients with DIPG as defined below.
Patients with newly diagnosed HGG (including diffuse hemispheric glioma, H3 G34-mutant; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; astrocytoma; IDH-mutant; or glioblastoma, IDH-wildtype): or non-pontine DMG (including diffuse midline glioma, H3 K27-altered; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; astrocytoma; IDH-mutant; or glioblastoma, IDH-wildtype) require histologic diagnosis.
Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential should use adequate contraception during study participation and for 6 months after the last dose of AZD1390. Male patients with female partners of childbearing potential should use adequate contraception during study participation and for 16 weeks after the last dose of AZD1390
Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible
Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible with the exception of corticosteroids
Anti-graft versus host disease (GVHD) agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial