Safety Study Of Avastin And Pelvic Radiation In Women With Recurrent Gynecological Cancers

The purpose of this research study is to learn the effects (good and bad) of an
antiangiogenic therapy drug (drugs that stop new blood vessel growth and starve a tumor by
cutting off its blood supply) called avastin. 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 bring nutrients to tumor
cells. In laboratory studies, avastin has been shown to inhibit the growth of several
different types of human cancer cells.

This drug has been studied in at least 3500 people with breast, colorectal, renal, ovarian
and lung cancer. It has not been studied in combination radiation therapy in people with
recurrent gynecological cancer.

Previous clinical trials involving the use of avastin in combination with standard radiation
in colorectal and pancreatic cancer show no significant increase in toxicity as compared to
standard radiation therapy toxicity.

The primary objective of this study is to assess the toxicity of administering avastin with
radiation for recurrent gynecological cancer. The secondary endpoint will be to assess the
time to progression of the disease. This means we hope this treatment program will delay any
regrowth of your cancer as compared to standard therapy with radiotherapy alone. In
addition, how well you respond to the treatment, patterns of remission or recurrence will be
measured.

Inclusion Criteria:

- All patients (age > 18 years) will have locally recurrent gynecological cancer with a
component of disease that will fit within a standard RT portal at the time of
presentation

- ECOG performance status score 0-1

- All patients will have had a prior hysterectomy

- Histological confirmation of recurrent gynecological cancer, including
adenocarcinoma, papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma

- Age > 18 years

- Radiologic work-up computer tomography of the chest and abdomen, and computer
tomography or MR of the pelvis confirming pelvis-confined recurrence

- Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL

- Adequate hepatic function as evidenced by:

Serum total bilirubin < 1.5 mg/dL SGOT/SGPT < 3X the ULN for the reference lab

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

Exclusion Criteria:

- Patients with a prior history of full course external beam radiation therapy to the
pelvis (patients with prior vaginal brachytherapy may be included)

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

- 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

- Known CNS disease (including history of encephalitis, multiple sclerosis or seizure
disorder), except for treated brain metastasis

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 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

- 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 (including history of encephalitis, multiple sclerosis or seizure
disorder)

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

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Any surgical procedure requiring an incision, open biopsy, or significant traumatic
injury within 28 days prior to study enrollment or anticipation of need for any
surgical procedure requiring an incision during the course of the study (excluding
vascular access device placement or procedures that do not require an incision)

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment

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

- 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).

- Known hypersensitivity to any component of avastin

- Any other medical condition, including mental illness or substance abuse, deemed by
the Investigator to be likely to interfere with a patient's ability to give informed
consent or cooperate and participate in the study or to interfere with the
investigator's ability to interpret the results