Phase II Study of Cetuximab and Bevacizumab in Esophageal Carcinoma That Failed First Line Therapy
1. Patients must have histologically or cytologically confirmed squamous cell carcinoma
or esophageal adenocarcinoma.
2. The disease must be recurrent after first line systemic therapy, with or without
radiation, with or without surgery.
3. Patients must be at least 1 month from prior chemotherapy or radiation therapy.
4. ECOG performance status ≤ 1 (Karnofsky > 60%)
5. Life expectancy of greater than 12 weeks.
6. Age > 18.
7. Patients must have normal bone marrow and other organ function or defined below:
- Absolute neutrophil count, > 1, 500/μL
- Platelet counts, > 100, 00/μL
_ Hemoglobin, > 8.0 gm/dL-
- Creatinine(< 1.5mg/dL)
8. No significant intercurrent medical illness (including NYHA class II, III or IV heart
disease, significant arrhythmias requiring medication, symptomatic coronary artery
disease, myocardial infarction within the previous 6 months.
9. Women of childbearing potential must have a negative pregnancy test.
10. Ability to understand and willingness to sign a written informed consent document.
I. Disease-specific Exclusions
1. All histologic types other than squamous cell carcinoma or adenocarcinoma.
2. Patients currently receiving other investigational agents, or who have received
3. Patients with known brain metastases.
4. History of severe allergic reactions attributed to compounds of similar chemical or
biologic composition to Cetuximab or Bevacizumab.
5. Patients with history of any other malignancy (except non-melanomatous skin cancer or
CIS of cervix) are ineligible unless a period of 5 years has lapsed since treatment
of the previous cancer and the patient has remained continuously disease free.
6. Patients who are felt to be poorly compliant.
7. Women who are breast-feeding.
II. General Medical Exclusions
Subjects meeting any of the following criteria are ineligible for study entry:
1. Inability to comply with study and/or follow-up procedures.
2. Life expectancy of less than 12 weeks.
3. Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study.
III. Bevacizumab-Specific Exclusions
1. Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure >100 mmHg on antihypertensive medications).
2. Any prior history of hypertensive crisis or hypertensive encephalopathy.
3. New York Heart Association (NYHA) Grade II or greater congestive heart failure
4. History of myocardial infarction or unstable angina within 6 months prior to study
5. History of stroke or transient ischemic attack within 6 months prior to study
6. Known CNS disease.
7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection).
8. Symptomatic peripheral vascular disease.
9. Evidence of bleeding diathesis or coagulopathy.
10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study.
11. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment.
12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment.
13. Serious, non-healing wound, ulcer, or bone fracture.
14. Proteinuria at screening as demonstrated by either
- Urine protein: creatinine (UPC) ratio ≥ 1.0 at screening OR
- 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. Known hypersensitivity to any component of bevacizumab.
16. Pregnant (positive pregnancy test) or lactating. Use of effective means of
contraception (men and women) in subjects of child-bearing potential.
17. History of myocardial infarction or unstable angina within 6 months of study