Clinical trial NCT00543842 (phase 1, status: completed)
Conditions: rectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: bevacizumab, capecitabine, erlotinib
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2
Eligibility criteria:

        Inclusion Criteria:

          1. Eastern Cooperative Oncology Group (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 MD Anderson Cancer
             Center (MDACC).

          4. Patients must have clinical stage II-III (T3, T4 or node-positive) based on computed
             tomography (CT), magnetic resonance (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 </= 7.5 mm. Criteria for pathologic enlargement of lymph nodes is >
             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 absolute neutrophil count (ANC) >/= 1500/L, platelets >/=
             100,000/mm^3, total serum bilirubin less than 2.0 mg%, blood urea nitrogen (BUN) </=
             30 mg%, creatinine </= 1.5 mg% and creatinine clearance >/= 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 vascular endothelial growth factor (VEGF) or epidermal growth factor receptor
             (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 intravenous (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. Aspartate aminotransferase or alanine aminotransferase (AST or ALT) >/= 2.5 times the
             upper limit of normal.

         11. Inability to swallow oral medication.

         12. Evidence of bleeding diathesis or coagulopathy, international normalized ratio (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 </= 1g of protein in 24 hours to be eligible).

         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