Trial of Vascular Endothelial Growth Factor (VEGF), Bevacizumab, in Combination With Cytotoxic Chemotherapy for Endometrial Cancer
Trial of Vascular Endothelial Growth Factor (VEGF), Bevacizumab, in Combination With Cytotoxic Chemotherapy for Endometrial Cancer
The purpose of this study is to find out whether the addition of a drug called Avastin
 (avastin) to the two-drug combination of carboplatin and paclitaxel shrinks tumors better
 than the two-drug combination alone in the treatment of endometrial cancer. Avastin is a
 humanized monoclonal antibody (a type of protein that is normally made by the immune system
 to help defend the body from infection and cancer) produced by Genentech, Inc. Avastin is an
 antibody directed against vascular endothelial growth factor, or VEGF. VEGF is a potent,
 specific growth factor with a well defined role in normal and abnormal blood vessel
 formation. It is present in a wide variety of normal tissues, but is produced in excess by
 most solid cancers (tumors). In the setting of cancer, VEGF promotes the growth of blood
 vessels that feed the tumor cells.
Exclusion Criteria

 Disease-Specific Exclusions

 -  Patients with a concomitant malignancy other than non-melanoma skin cancer. Patients
 with a prior malignancy who have been disease-free for greater than 5 years or who
 received prior chemotherapy for that malignancy.

 -  Patients in whom pathological confirmation of the tumor is not obtainable. General
 Medical Exclusions

 -  Patients with concomitant medical illness such as serious uncontrolled infection,
 uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the
 treating physician, make the treatments prescribed on this study unreasonably hazardous
 for the patient.

 -  Patients with third degree or complete heart block are not eligible unless a pacemaker
 is in place. Patients on medications which alter cardiac conduction, such as digitalis,
 beta-blockers, or calcium channel blockers, or who have other conduction abnormalities
 or cardiac dysfunction may be placed on study at the discretion of the investigator.

 -  Patients whose circumstances will not permit study completion or adequate follow-up.

 -  Patients who are sensitive to E. Coli-derived drug preparations.

 -  Life expectancy of less than 12 weeks.

 -  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 avastin
 cancer study.

 -  Inadequately controlled hypertension (defined as systolic blood pressure greater than
 150 and/or diastolic blood pressure greater than 100 mmHg on antihypertensive
 medications).

 -  Any prior history of hypertensive crisis or hypertensive encephalopathy.

 -  New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
 Appendix C).

 -  History of myocardial infarction or unstable angina within 6 months prior to study
 enrollment.

 -  History of stroke or transient ischemic attack within 6 months prior to study
 enrollment.

 -  Known CNS disease.

 -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection). Symptomatic
 peripheral vascular disease

 -  Evidence of bleeding diathesis or coagulopathy. Blood coagulation parameters: PT such
 that international normalized ratio (INR) is less than 1.5 (or an in range INR, between
 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT less than
 1.5 times the institutional upper limit of normal.

 -  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.

 -  Core biopsy or other minor surgical procedure, excluding placement of a vascular access
 device, within 7 days prior to study enrollment.

 -History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess
 within 6 months prior to study enrollment. Patients with clinical symptoms or signs of
 gastrointestinal obstruction and who require parenteral hydration and/or nutrition.

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

 -  Proteinuria at screening as demonstrated by:

 -  Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening

 -  Known hypersensitivity to any component of avastin.

 -  Pregnant (positive pregnancy test) or lactating. Refusal to use of effective means of
 contraception (men and women) in subjects of child-bearing potential.
Inclusion Criteria:

 -  Patients must have histologically confirmed primary Stage III or Stage IV (see FIGO
 staging-Appendix I) or recurrent endometrial carcinoma with MEASURABLE disease whose
 potential for cure by radiation therapy or surgery alone or in combination is very
 poor. Recurrent disease must be biopsy confirmed.

 -  Patients may have received prior cytotoxic chemotherapy

 (1 therapy) excluding a platinum/taxane. Patients may have received prior hormonal
 therapy or therapy with biologic agents, but such therapies must be discontinued 4
 weeks prior to entry on this study.

 -  Patients in whom both radiation and chemotherapy is planned may receive radiation
 prior to entry on this study (order not specified). At least four weeks should have
 elapsed since completion of RT involving the whole pelvis or over 50% of the spine.

 -  Patients must be 18 years of age or older.

 Exclusion Criteria:

 -  Patients with a concomitant malignancy other than Genentech, Inc Page 27 of 62
 Bevacizumab Protocol 03-10-08 Page 27 non-melanoma skin cancer. Patients with a prior
 malignancy who have been disease-free for < 5 years or who received prior chemotherapy
 for that malignancy.

 -  Patients in whom pathological confirmation of the tumor is not obtainable.

 -  Patients with concomitant medical illness such as serious uncontrolled infection,
 uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the
 treating physician, make the treatments prescribed on this study unreasonably
 hazardous for the patient.

 -  Patients with third degree or complete heart block are not eligible unless a pacemaker
 is in place. Patients on medications which alter cardiac conduction, such as
 digitalis, beta-blockers, or calcium channel blockers, or who have other conduction
 abnormalities or cardiac dysfunction may be placed on study at the discretion of the
 investigator.

 -  Life expectancy of less than 12 weeks.

 -  Patients who are sensitive to E. Coli-derived drug preparations.

 -  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.