Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors

Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV.

Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first
3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4
will be an escalation of irinotecan to 150 mg/m2.

For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO.
Doses will be escalated according to standard phase I dose escalation criteria.

Inclusion Criteria:

- Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible.
Other central nervous system tumors may be considered for treatment at discretion of
investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic
pathway tumor.

- The patient should have failed first line therapy and be considered refractory,
relapsed, or recurrent. Exceptions are high grade gliomas including brain stem
gliomas.

- Age 18 months though age 23 years are eligible for this protocol.

- The patient may have received any of the agents, but not in this combination. Patients
will not be eligible if they have received the combination of bevacizumab and IV
irinotecan as prior therapy. They will not be eligible if they had progressive disease
on any of these agents. Investigator discretion may also be used.

- Bone marrow should be recovered from prior therapy with ANC >1500 and platelets
>100,000.

- Serum creatinine should be less than institutional upper limit of norm.

- ALT/AST <3 times normal and bilirubin <1.5 times normal.

- Neurologic symptoms should be stable for 1 week with stable or decreasing doses of
steroids.

- Patients should not be pregnant or breast feeding.

Exclusion Criteria:

- Patients with bleeding disorders or on anticoagulants.

- Uncontrolled hypertension.

- Other risks of bleeding determined on individual basis.

- Patients receiving enzyme inducing anticonvulsants.

- Patients with significant cardiac or pulmonary dysfunction that would compromise the
patient's ability to tolerate protocol therapy or would likely interfere with the
study procedures or results.

- For patients receiving bevacizumab, those who have had surgical procedures should not
receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate
procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines
are not considered minor procedures and may occur at any time prior to or during
therapy.