Phase I Study of Bevacizumab and Sorafenib Combined With Low Dose Cyclophosphamide in Patients With Refractory Solid Tumors and Leukemia

Inclusion Criteria:

- Diagnosis: Solid tumors, including central nervous system tumors and lymphomas, that
are recurrent or refractory to standard therapy or for which there is no standard
therapy. Histologic verification of diagnosis is required.

- Age: < or = 21 years of age at the time of original diagnosis

- Life expectancy: at least 8 weeks

- Performance status: Karnofsky > or = 50 for > 10 years of age; Lansky > or = 50 for
children < or = 10 years of age.

- Organ Function: Must have adequate organ and marrow function

- Prior Therapy: Patient must have fully recovered from the acute toxic effects of all
prior therapy prior to enrolling on study.

- Must not have current or recent use of full-dose anticoagulants

- Must not have received medications known to inhibit platelet function or known to
selectively inhibit cyclooxygenase-2 (COX-2) activity

- Bevacizumab and sorafenib should not be administered to pregnant women.

- Pregnancy tests must be obtained in girls who are > 10 years of age or
post-menarchal.

- Males or females of reproductive potential may not participate unless they have
agreed to use an effective contraceptive method.

- Breast feeding should be discontinued if a mother wishes to participate in this
study.

- Patients with a documented, chronic non-healing wound, ulcer, or bone fracture or
history of a major surgical procedure or significant traumatic injury within 28 days
prior to beginning therapy should be excluded due to preclinical evidence supporting
the potential for delayed wound healing.

- Patients must not have a deep venous or arterial thrombosis (including pulmonary
embolism) within the last three months prior to study entry, and must not have a
known thrombophilic condition

- Patients must not have a history of myocardial infarction, severe or unstable angina,
or severe peripheral vascular disease.

- Ability to understand and willingness of research participant or legal
guardian/representative to give written informed consent.

Exclusion Criteria:

- Body surface area < 0.3 m2

- Presence of a known bleeding diathesis or coagulopathy

- Patients with evidence of intra-tumoral central nervous system hemorrhage. in current
scans. Patients are required to have a head CT or MRI within 2 weeks prior to study
enrollment.

- Patients with known hypersensitivity to other recombinant human antibodies

- Patients who have an uncontrolled infection

- Patients with recurrent or refractory leukemia will be excluded from the dose
escalation component of the phase I trial.