A. Screening Criteria:

        Subject must have a diagnosis of medulloblastoma that is recurrent or refractory and must
        have adequate tissue for SHH subgrouping.

        B. Inclusion Criteria:

          1. Phase I Skeletally-immature:

             a. Patient must be skeletally-immature at the time of study enrollment, defined as
             females with a bone age < 14 years and males with a bone age < 16 years. Patient must
             be ≥3 and ≤18 years of age and BSA must meet protocol restrictions.

          2. Phase II Skeletally-mature:

               1. Patients must be skeletally-mature, defined as females with a bone age ≥14 years
                  and males with a bone age ≥ 16 years OR have a chronological age >18 years.

               2. Must have bi-dimensionally measurable disease

          3. Surgical Study:

               1. Surgical resection must be clinically indicated.

               2. Must be ≥3 years.

               3. Must be amenable to receiving CX-4945 for 5-7 days prior to surgery

          4. All Phases:

               1. Must have a diagnosis of SHH medulloblastoma that is recurrent or progressive
                  which was confirmed histologically and subgrouping was completed using a CLIA
                  certified methylation based test.

               2. Prior Therapy

                    -  Must have received prior therapy which included radiation therapy and
                       recovered from acute treatment related toxicities.

                    -  Must have received the last dose of myelosuppressive therapy at least 21
                       days prior to enrollment and at least 42 days if nitrosourea.

                    -  Must have received the last dose of another investigational or biologic
                       agent ≥7 days prior. For agents known to have adverse events occurring
                       beyond 7 days, the period must be extended to accommodate the longer
                       interval. For monoclonal antibodies with prolonged half-lives, at least 3
                       half-lives must have elapsed.

                    -  Must have received last fraction of craniospinal or total body irradiation
                       or radiation to ≥50% of the pelvis >3 months prior to enrollment. Last
                       fraction of focal irradiation must be >4 weeks prior to enrollment.

                    -  Must be ≥ 6 months since allogeneic stem cell transplant with no evidence of
                       acute graft vs. host disease.

                    -  Must be ≥3 months since autologous stem cell transplant.

               3. Must be off all colony-forming growth factors at least 1 week prior to
                  enrollment. Must be off 2 weeks if the subject received a long-acting
                  formulation.

               4. If neurological deficits are present, must have been stable for a minimum of 1
                  week prior to enrollment.

                  • Patients with seizure disorders may be enrolled if seizures are well
                  controlled.

               5. Must have a Karnofsky/Lansky Performance status ≥50%

               6. Must have adequate organ and marrow function

               7. Subjects receiving dexamethasone must be on a stable or decreasing dose for at
                  least 1 week prior to enrollment.

               8. Female patients of childbearing potential must have a negative pregnancy test.

               9. Patients of child-bearing or child fathering potential must be willing to use
                  medically acceptable form of birth control while treated on this study and for 3
                  months after drug cessation.

              10. Parent or legal guardian must be able to understand and willing to sign the
                  written informed consent.

        C. Exclusion Criteria:

        1. All Phases

          1. Nursing mothers due to an unknown but potential risk for adverse events in nursing
             infants.

          2. Patients with a history of any other malignancy with the exception of patients with a
             secondary brain tumor if the patient's prior malignancy has been in remission for at
             least 5 years from the end of treatment.

          3. Patients with any of the following gastrointestinal disorders - difficulty swallowing
             or active malabsorption, uncontrolled diarrhea, gastritis, ulcerative colitis, Crohn's
             disease or hemorrhagic coloproctitis, history of gastric or small bowel surgery
             involving any extent of gastric or small bowel resection.

          4. Patients with any clinically significant unrelated systemic illness that would
             compromise the patient's ability to tolerate therapy, put them at additional risk for
             toxicity or interfere with the study procedures or results.

          5. Corrected QT (QTc) interval is >480ms

          6. Patients who are receiving other anti-cancer or investigational drug therapy

          7. Patients who are on warfarin or statins.