A Randomized Placebo-Controlled Study of Perifosine in Combination With Single Agent Chemotherapy for Metastatic Cancer Patients

Inclusion Criteria:

1. In the opinion of the treating physician, treatment with one of the following
regimens should represent an appropriate treatment for the patient.

- Capecitabine 825 mg/m2 BID days 1 - 14 q 3 weeks

2. Patients should have a histologically or cytologically confirmed diagnosis of
colorectal cancer.

3. Patients must have received at least one but no more than two prior chemotherapy
regimen(s) for the treatment of metastatic or recurrent disease.

4. ECOG performance status 0 or 1.

- Leukocytes >= 4,000/μL

- absolute neutrophil count >= 1,500/ μL

- platelets >= 100,000/ μL

- HCT > 28% (with or without growth factor support)

- Creatinine <= 2.5 mg/dl

- total bilirubin < 1.5 x upper limit of normal

- transaminase < 2.5 x upper limit of normal

5. Patients must have recovered from acute toxicity—excluding alopecia—related to prior
therapy, including surgery or radiotherapy.

6. Patients with brain metastases may be admitted, provided the disease has been treated
and been stable for 2 months.

7. Patients must have ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

1. Patients receiving any other investigational agents or devices.

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to perifosine (miltefosine or edelfosine).

3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, psychiatric illness, or social situations that would limit compliance with
study requirements.

4. HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study due to potential pharmacokinetic interactions with perifosine.

5. Patients with a history of unstable or newly diagnosed angina pectoris, recent
myocardial infarction (within 6 months of enrollment), or New York Heart Assoc. class
II - IV congestive heart failure.

6. Female patients who are pregnant or lactating are ineligible.