Phase I/II Trial of Preoperative Radiotherapy With Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Rectal Cancer

Inclusion Criteria:

1. ECOG performance status of 0 or 1.

2. Patients must be >/= 18 years of age.

3. All patients must have histologically confirmed adenocarcinoma of the rectum with
pathologic material reviewed by the Department of Pathology at MDACC.

4. Patients must have clinical stage II-III (T3, T4 or node-positive) based on CT, MR or
endoscopic ultrasound criteria.

5. Patients must have no distant metastatic disease on chest, abdomen and pelvic CT scan
performed with IV contrast. If the CT was performed outside of MDACC, the slice
thickness must be
15 mm on short axis dimension.

6. The rectal tumor must be either palpable on digital rectal exam or the inferior edge
of the tumor must be within 12 cm of the anal verge based on rigid proctoscopy.

7. Patients must have ANC >/= 1500/L, platelets >/= 100,000/mm^3, total serum bilirubin
less than 2.0 mg%, BUN >/= 30ml/min (estimated as calculated with Cockcroft-Gault equation). Note: In
patients with moderate renal impairment (estimated creatinine clearance 30-50 mL/min)
at baseline, a dose reduction to 75% of the capecitabine starting dose is
recommended.

8. Hemoglobin >/= 9 gm/dL (may be transfused to maintain or exceed this level).

9. Patients must have signed informed consent indicating that they are aware of the
investigational nature of the study, and are aware that participation is voluntary.
Patients must be made aware of their other treatment options.

Exclusion Criteria:

1. Prior radiotherapy to the pelvis.

2. Any prior chemotherapy.

3. Prior VEGF or EGFR-directed therapy, such as bevacizumab, cetuximab, erlotinib, or
gefitinib.

4. Current, prior or planned participation in any other experimental drug study.

5. Pregnant or lactating woman. Woman of childbearing potential with either a positive
or no pregnancy test at baseline. Women / men of childbearing potential not using a
reliable contraceptive method (oral contraceptive, other hormonal contraceptive,
intrauterine device, diaphragm or condom). (Postmenopausal woman must have been
amenorrheic for at least 12 months to be considered of non-childbearing potential).
Patients must agree to continue contraception for 30 days from the date of the last
study drug administration.

6. Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics.

7. Treatment for other clinically significant cancers within the last five years, except
cured non-melanoma skin cancer and treated in-situ cervical cancer.

8. Inadequately controlled hypertension [systolic blood pressure of >130 and/or
diastolic blood pressure of >90 mmHg on antihypertensive medication at time of study
entry and/or at time of starting therapy] history of myocardial infarction or
unstable angina within 12 months prior to study enrollment, New York Heart
Association Class II or greater congestive heart failure, unstable symptomatic
arrhythmia requiring medication (subjects with chronic atrial arrhythmia i.e., atrial
fibrillation or paroxysmal supraventricular tachycardia are eligible) or Class II or
greater peripheral vascular disease

9. History of stroke or transient ischemic attack at any time,history of hypertensive
crisis or hypertensive encephalopathy.

10. AST or ALT >/= 2.5 times the upper limit of normal.

11. Inability to swallow oral medication.

12. Evidence of bleeding diathesis or coagulopathy, INR >/= 2.5.

13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study; fine needle aspirations or core biopsies within 7 days prior to
Day 0.

14. Proteinuria at baseline or clinically significant impairment of renal function as
demonstrated by either a. Urine protein:creatinine ratio >/= 1.0 at screening. b.
Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria
on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must
demonstrate
15. Current serious, nonhealing wound, ulcer, or bone fracture.

16. History of aortic aneurysm > 4.5 or aortic dissection.

17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0.

18. Patients who have had an organ allograft.

19. Patients on Coumadin are recommended to be changed to Low Molecular Weight Heparin
(LMWH) at least 1 week prior to starting capecitabine. If patients cannot be switched
to LMWH, then extra monitoring of their International Normalized Ratio (INR) will be
performed.

20. Patients taking Sorivudine or Brivudine must be off of these drugs for 4 weeks.
Patients taking cimetidine must have this drug discontinued. Ranitidine or a drug
from another anti-ulcer class can be substituted for cimetidine if necessary. If
patient is currently receiving allopurinol, must discuss with PI to see of another
agent may substitute for it.

21. Patients with known Gilberts disease will be considered ineligible due to potential
UGTA1 polymorphism effects on metabolism for erlotinib.

22. Inability to comply with study and/or follow-up procedures.

23. Known hypersensitivity to any component of bevacizumab, erlotinib or capecitabine

24. Prior history of hypertensive crisis or hypertensive encephalopathy

25. Peripheral arterial thrombosis within 6 months prior to study enrollment