Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases

Standard of care for treatment of patients with brain metastases, which are considered not
surgically removable, is radiation therapy to the brain lesions. This treatment is called
Fractionated Stereotactic Radiotherapy (FSRT) and is given without chemotherapy and usually
over 5 days.

Researchers of this study want to find out if adding an investigational drug, called TPI 287,
to standard radiation therapy (FSRT) can help people with brain metastases from cancer. TPI
287 is a drug that is being tested and is not approved for sale in the United States by the
U.S. Food and Drug Administration (FDA).

Inclusion Criteria:

- Must have histologically or cytologically confirmed non-central nervous system primary
solid malignancy.

- Must have pathologically or radiologically confirmed metastatic disease in the brain.

- Potential participants with up to 3 brain metastases (symptomatic and non-symptomatic)
can be treated on this study. Maximum diameter of each brain lesion should be ≤ 5 cm.
Maximum tumor volume ≤ 120 cc.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%).

- Life expectancy of greater than 12 weeks.

- Patients requiring treatment with corticosteroids are eligible.

- Treatment with non-enzyme inducing anti-seizure medications is allowed.

- Must have normal organ and marrow function.

- Systemic chemotherapy washout period ≥ 7 days. For investigational dugs and monoclonal
antibodies washout period ≥ 5x drug half-life. There are no limitations on number of
prior treatment regimens.

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while she or her partner is participating
in this study, she should inform her treating physician immediately. Men treated or
enrolled on this protocol must also agree to use adequate contraception prior to the
study, for the duration of study participation, and 4 months after completion of TPI
287 administration.

- Prior brain surgery or radiation is allowed as long as the metastatic lesion(s) to be
targeted in this study has not previously been treated with radiation.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Patients who have had chemotherapy within 1 week (6 weeks for nitrosoureas or
mitomycin C) or investigational therapies/monoclonal antibodies within 5 half-life of
investigational compound or those who have adverse events which are greater than grade
1 and are due to agents administered more than 1 week earlier. Bisphosphonates,
endocrine therapy, and trastuzumab are permitted without restriction.

- Are receiving any other investigational agents.

- Previous treatment of the target lesions with radiation therapy.

- Have previously been treated with whole brain radiation.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to TPI 287.

- Have brain metastases secondary to germ cell tumor or lymphoma malignancy.

- Women who are pregnant or nursing (lactating).

- Known contraindication to enhanced MRI and CT scan.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled seizure activity or psychiatric illness/social situations
that would limit compliance with study requirements.