A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy

This protocol is for a Phase 1 safety lead-in clinical trial of BMX-001 in combination with
WBRT in 5 patients with MBM. Demonstrating safety of the selected MTD of BMX-001 in patients
with MBM undergoing standard protocol WBRT will be the "go/no-go" criteria for proceeding to
Phase 2. Phase 2 is a randomized open-label Phase 2 clinical trial of 64 patients with MBM,
half receiving BMX-001 in combination with WBRT and half receiving WBRT alone.

Subjects are treated with BMX-001 for a total of 19 days, during which time they receive
radiation therapy. Following completion of radiation therapy, subjects will be followed for
an additional one year.

Inclusion Criteria:

- Subjects must have histologically confirmed diagnosis of a non-small cell lung cancer,
breast cancer, melanoma or renal cell cancer primary

- Subjects must have >10 contrast-enhancing lesions, never previously treated with SRS
and/or surgical resection, on a contrast-enhanced T1-weighted brain MRI performed
within two weeks of enrollment, with at least one lesion >0.5cm in greatest dimension

- Physical examination by a radiation oncologist or medical oncologist within 14 days of
the start of WBRT

- Plan to be treated with WBRT to a dose of 30 Gy in 10 fractions

- Age * 18 years

- Karnofsky Performance Status (KPS) ≥ 70

- Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/*l, platelets ≥ 125,000 cells/*l

- Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of
normal

- Signed informed consent approved by the Institutional Review Board

- If sexually active, patients must agree to use appropriate contraceptive measures for
the duration of the study and for 6 months afterwards as stated in the informed
consent

- Able to provide study specific informed consent

- Willing to follow study procedures, complete QOL questionnaires and neurocognitive
testing as described in the protocol

- Negative serum pregnancy test for women of child bearing potential within 48 hours of
first dose of BMX

Exclusion Criteria:

- Active infection requiring IV antibiotics 7 days before enrollment

- Hypertension requiring 3 or more anti-hypertensive medications to control

- Requirement for concurrent treatment with nitrates or other drugs that may, in the
judgment of the treating investigator, create a risk for a precipitous decrease in
blood pressure

- History of syncope within the last 6 months

- Subjects receiving prohibited medications listed in Section 6.4.2 of this protocol are
not eligible. Subjects who can safely stop taking a prohibited medication at least 7
days prior to the first dose of BMX may participate at the discretion of the treating
physician.

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

- Women who are breast feeding

- Known hypersensitivity to compounds of similar chemical composition to BMX-001

- Prior surgical resection for brain metastases and/or stereotactic radiosurgery for up
to 5 brain metastases in total are permitted if performed at least 1 month prior to
planned WBRT under this protocol.

- Prior whole brain radiation therapy

- Patients with diffuse leptomeningeal disease (carcinomatous meningitis)