Stereotactic Body Radiation With Nelfinavir for Oligometastases

The use of radiation therapy to treat metastatic tumors is well established and promising
data are emerging with the use of SBRT for metastatic disease. However, the use of a single
large fraction concurrent with a radiosensitizer as is being proposed is not of proven
benefit. This investigation aims to confirm the safety and efficacy for SBRT used
concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose
selected has been chosen with the belief that it is safe and effective based on prior
experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients
will be treated with a single fraction (per lesion site), targeted to the lesion concurrently
with the radiosensitizer Nelfinavir.

On the basis of this preclinical evidence, we propose a phase II study of Nelfinavir combined
with SBRT in patients with oligometastatic disease. Because the standard dose of Nelfinavir
for HIV patients is known to be safe and does inhibit the phosphorylation of Akt and decrease
tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of SBRT. Experience
with single-fraction pulmonary and pancreas SBRT provides a useful dose for this trial. With
published data establishing the relative safety of large single-fraction SBRT to the lungs
and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT concurrently
with the radiosensitizer Nelfinavir. Once this is established, we propose to continue to
enroll more patients to the study at this dose to determine the efficacy of this type of
therapy.

The proposed study represents an informed estimate based on current knowledge of SBRT doses
and those administered in currently approved image-guided protocols (brain, base of skull,
cervico-thoracic spine, pancreas and liver). This study will refine the current understanding
of single fraction radiation tolerance for normal tissues, thereby making it possible to
treat future patients more safely and aggressively.

Inclusion Criteria

- Patient's tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3

- Patient must have metastasis at one or more of the following sites: bone, liver, lymph
node and/or lung. No more than five lesions will be treated.

- Histological confirmation of malignancy (primary or metastatic tumor).

- Patient may have any prior therapy allowed aside from having had prior radiotherapy to
the treatment site (see exclusion criteria 5.2.3).

- Patient must be ≥ 18 years of age.

- Patient must have a life expectancy ≥ 9 months.

- Patient must have an ECOG performance status ≤ 2.

- Patient must have normal organ and marrow function.

- Patient must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering
the study

- Patients receiving any other investigational agents

- Pateitnw ho has had any prior radiotherapy to the treatment site(s)

- Patients taking drugs that are contraindicated with nelfinavir, including any of the
following:

Amiodarone, Quinidine, Rifampin, Dihydroergotamine, Ergonovine, Ergotamine,
Methylergonovine, Hypericum perforatum (St. John's wort), Lovastatin, Simvastatin,
Pimozide, Midazolam, Triazolam

- Women of child bearing potential who refuse to take a pregnancy test prior to
treatment

- Participation in another concurrent treatment protocol while being treated on this
protocol and through to 3 months after treatment on this protocol has ended

- Pregnant women

- Inability to understand the informed consent document

- Inability to sign the informed consent document

- Poor liver function suggestive of cirrhosis or steatohepatitis