Testing the Safety and Tolerability of CX-4945 in Patients With Recurrent Medulloblastoma Who May or May Not Have Surgery

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.