XAD - Xelox (Capecitabine + Oxaliplatin) + Bevacizumab + Dasatinib

Inclusion Criteria:

Criteria Specific for Dose Escalation (Phase I)

1. Patients must have histologically confirmed solid tumor malignancy that is metastatic
or unresectable and for which standard curative or palliative measures do not exist
or are no longer effective, or for whom capecitabine, oxaliplatin, and/or bevacizumab
would be considered a standard therapy or therapeutic option.

2. Patients must not have had radiation therapy, hormonal therapy, biologic therapy or
chemotherapy for cancer within the 28 days prior to study day 1.

Criteria Specific for Expanded Cohort Portion of Trial Only

1. Histologically documented adenocarcinoma of the colon or rectum that is
metastatic/recurrent disease

2. No prior chemotherapy for metastatic/recurrent colorectal cancer. Patients may have
received a radiosensitizing dose of 5-fluorouracil or capecitabine for the treatment
of local disease in the localized or metastatic setting.

3. No history of other carcinomas within the last five years, except cured non-melanoma
skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer

4. Disease must be measurable by Response Evaluation Criteria In Solid Tumors (RECIST)
criteria

Inclusion Criteria for All Participants

1. Age >18 years.

2. Karnofsky performance status > 70%.

3. Life expectancy of at least 3 months.

4. Patients must have adequate organ and marrow function as defined below:

5. Sexually active women of childbearing potential must use an effective method of birth
control during the course of the study, in a manner such that risk of failure is
minimized.

6. All women of child bearing potential (WOCBP) MUST have a negative pregnancy test
within 7 days prior to first receiving investigational product.

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

Exclusion Criteria for ALL Subjects:

1. Patients who have had radiation therapy, hormonal therapy, biologic therapy, or
chemotherapy for cancer within the 28 days prior to day 1 of the study (ie - first
day of study drug treatment).

2. Patients who have received any other investigational agents within the 28 days prior
to day 1 of study drug treatment.

3. Patients with known central nervous system (CNS) metastases.

4. Inadequately controlled hypertension

5. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

6. Symptomatic peripheral vascular disease

7. Evidence of bleeding diathesis or coagulopathy. Patients on full-dose anticoagulation
are permitted to enroll provided that they have been clinically stable on anti-
coagulation.

8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to day 1 of study drug treatment

9. Core biopsy or other minor surgical procedure excluding placement of a vascular
access device, within 7 days prior to expected start of treatment.

10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study day 1

11. Serious, non-healing wound, ulcer, or bone fracture

12. Proteinuria at screening

13. Any prior history of hypertensive crisis or hypertensive encephalopathy

14. New York Heart Association (NYHA) Grade II or greater congestive heart failure

15. History of myocardial infarction, unstable angina, cardiac or other vascular
stenting, angioplasty, or surgery within 6 months prior to study treatment day 1

16. History of stroke or transient ischemic attack within 6 months prior to study
treatment day 1

17. History of intolerance or hypersensitivity to prior treatment with capecitabine,
oxaliplatin, bevacizumab and/or dasatinib.

18. No previous treatment with dasatinib.

19. Prior unanticipated severe reaction to fluoropyrimidine therapy, or known
hypersensitivity to 5-fluorouracil, or known dihydropyrimidine dehydrogenase (DPD)
deficiency.

20. Patient with grade 2 or greater peripheral neuropathy

21. Chronic treatment with systemic steroids or another immunosuppressive agent.

22. Other concurrent severe and/or poorly controlled medical condition that could
compromise safety of treatment as so judged by treating physician.

23. A known history of HIV seropositivity,hepatitis C virus, acute or chronic active
hepatitis B infection, or other serious chronic infection requiring ongoing
treatment.

24. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel
resection)

25. Patients unwilling to or unable to comply with the protocol

26. Diagnosed or congenital long QT syndrome

27. Any history of clinically significant ventricular arrhythmias

28. Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)

29. Pleural effusion grade > 2.

30. Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes including:

31. History of significant bleeding disorder unrelated to cancer

32. Patients actively taking proton pump inhibitors or H2 antagonists will be excluded
from this study.

33. Any psychiatric illness/social situations that would limit safety or compliance with
study requirements

34. Medications that inhibit platelet function (except low dose aspirin as defined in
study protocol)

35. Use of medications that are either Cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers