Inclusion Criteria:

          -  Patients with newly diagnosed DIPG by MRI; defined as patients with a pontine location
             and diffuse involvement of at least 2/3 of the pons are eligible without histologic
             diagnosis. For lesions with typical imaging features, biopsy is neither encouraged nor
             required for eligibility. Tumors that are biopsied will be eligible if proven to be
             supportive of the diagnosis of a DIPG. Consensus of diagnosis by the study team must
             be met.

          -  Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after,
             the date of the completion of focal radiotherapy.

          -  Prior Chemotherapy: Patients should be at least 30 days from last chemotherapy dose
             prior to start of CED infusion, with exception of antibody half-lives. For antibody
             therapies, at least 3 half-lives of the antibody after last dose of monoclonal
             antibody should have passed prior to CED infusion. Patients less than 30 days from
             last chemotherapy dose should be discussed with the study chair(s).

          -  Prior Radiation: Patients must have completed prior treatment with standard focal
             radiotherapy as part of initial treatment for DIPG and had their last dose at least 4
             weeks prior to and no later than 14 weeks from the first CED treatment. Patients
             beyond 14 weeks from radiation therapy but with stable disease should be discussed
             with the study chair.

          -  Age ≥ 2 years of age. Patients younger than 3 years of age may be enrolled on study at
             the discretion of the Study Chair(s) if supporting evidence that brainstem lesion
             represents a brainstem glioma.

          -  Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients 16 years of
             age and younger. Patients who are unable to walk because of paralysis, but who are up
             in a wheelchair, will be considered ambulatory for the purpose of assessing the
             performance score.

          -  Life expectancy of greater than 12 weeks measured from the date of completion of
             radiotherapy.

          -  Corticosteroids: Patients who are receiving dexamethasone must be on a stable or
             decreasing dose for at least 1 week prior to registration.

          -  Organ Function Requirements

               -  Adequate Bone Marrow Function Defined as:Peripheral absolute neutrophil count
                  (ANC) ≥1000/mm3 and platelet count ≥ 100,000/mm3 (transfusion independent,
                  defined as not receiving platelet transfusions for at least 7 days prior to
                  enrollment) and normal coagulation defined as normal international normalized
                  ratio (INR) or per institutional guidelines.

               -  Adequate Renal Function Defined as:

                    -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70
                       milliliters (mL)/min/1.73 m2 or

                    -  A serum creatinine based on age/gender as follows:

        Age Maximum Serum Creatinine (mg/dL) Male Female 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1
        10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

        ≥ 16 years 1.7 1.4

          -  Adequate Liver Function Defined as: Bilirubin (sum of conjugated + unconjugated) less
             than or equal to 1.5 x upper limit of normal (ULN) for age and serum glutamate
             pyruvate transaminase (SGPT) (ALT) less than or equal to 110 U/L. and Serum albumin ≥
             2 g/dL.

          -  Adequate Neurologic Function Defined as: Patients with seizure disorder may be
             enrolled if on non-enzyme inducing anticonvulsants and well controlled.

               -  The effects of irinotecan liposome injection on the developing human fetus are
                  unknown. For this reason women of child-bearing potential and men must agree to
                  use adequate contraception (hormonal or barrier method of birth control;
                  abstinence) prior to study entry, for the duration of study participation and 4
                  months after completion of irinotecan liposome injection administration. Should a
                  woman become pregnant or suspect she is pregnant while she or her partner is
                  participating in this study, she should inform her treating physician
                  immediately.

               -  A legal parent/guardian or patient must be able to understand, and willing to
                  sign, a written informed consent and assent document, as appropriate

        Exclusion Criteria:

          -  Patients who had clinical and/or radiographic (MRI) progression of tumor following
             external beam radiation therapy.

          -  Patients with metastatic disease, including leptomeningeal or subarachnoid
             disseminated disease.

          -  Patients with tumor morphology or other imaging findings that predict poor coverage of
             the majority of the tumor including significant tumor volume outside the pons or
             presence of large cysts within the tumor that would prevent adequate tumor coverage by
             CED. Patients with concern for adequate tumor coverage based on tumor morphology
             should be discussed with the study chairs.

          -  Patients who are receiving any other tumor-directed therapy

          -  Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded;
             the patients should be discussed with the study chair(s) and study neurosurgeon prior
             to any planned CED treatment.

          -  Untreated symptomatic hydrocephalus determined by treating physician.

          -  Patients should not be on enzyme-inducing anticonvulsants or other drugs that might
             interact with the cytochrome P450 enzyme system. If previously on an enzyme-inducing
             anti-epileptic drug (EIAED), patients should be off for at least 10 days prior to CED
             infusion and discussed with the Study Chair.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to irinotecan, topotecan, gadolinium, or lipids.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Female patients of childbearing potential must not be pregnant or breast-feeding.
             Female patients of childbearing potential must have a negative serum or urine
             pregnancy test within 14 days of registration.

          -  Patients who are unable to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy. Telemedicine visits are acceptable.