Avastin in Patients With Epithelial Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer

OBJECTIVES:

Primary:

To determine the activity of bevacizumab in patients with epithelial ovarian, primary
peritoneal serous, papillary serous endometrial or fallopian tube cancer who relapse after
achieving an initial complete response to first-line therapy that included at least 6 month
bevacizumab maintenance as defined by: 1) clinical response rate OR 2) clinical benefit
response

Secondary:

- To assess duration of progression free survival (PFS)

- To assess the safety

- To correlate response with the Avastin-free interval

STATISTICAL DESIGN:

This study used a two-stage design to evaluate efficacy of bevacizumab based on a patient
achieving either clinical response or clinical benefit response. The null and alternative
response rates were 10% and 30%. If two or more patients enrolled in the stage one cohort
(n=10 patients) achieved response than accrual would proceed to stage two (n=19 patients). If
response was achieved by at least 6 patients in the final set of 29 evaluable patients then
bevacizumab would be deemed worthy for further study. This design had 80% power given
one-sided 0.05 significance level.

Inclusion Criteria:

- Histologically or cytologically confirmed epithelial ovarian cancer, primary
peritoneal serous cancer, papillary serous endometrial cancer, or fallopian tube
cancer

- Must have responded and remained clinically stable (as defined by normal clinical
examination, normal serum CA125 level and normal CT scan) after first-line
platinum-based regimen followed by bevacizumab maintenance therapy

- Must have developed relapsed disease at least 3 months after completion of bevacizumab
maintenance therapy as defined by a) development of new, measurable lesions by RECIST
criteria, but no lesion with maximum diameter greater than 3 centimeters OR b) newly
elevated CA125 level at least 2 x ULN on 2 separate occasions, obtained at least 1 day
but not more than 3 months apart

- ECOG Performance Status 0-2

- No prior cytotoxic chemotherapy or biologic therapy for disease recurrence allowed

- Prior hormonal-based therapy for ovarian, primary peritoneal serous or fallopian tube
cancer is allowed

- Toxic side effects related to prior chemotherapy or hormonal therapy must have
resolved to grade one or less or to baseline before initiation of bevacizumab

- 18 years of age or older

- Life expectancy of 6 months or greater

- Normal organ and marrow function as outlined in the protocol

Exclusion Criteria:

- Prior cytotoxic chemotherapy or biologic therapy for disease recurrence

- Known CNS disease, except for treated brain metastasis

- Pregnancy or breast feeding

- Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- 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

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

- History of abdominal fistula, GI perforation, intra-abdominal abscess, or CT evidence
of bowel obstruction or bowel wall thickening

- Symptoms of intestinal obstruction, or requirement of parenteral hydration and/or
nutrition

- History of active malignancy during the last 3 years, except non-melanomatous skin
cancer or in situ breast or cervical cancer

- Evidence of preexisting uncontrolled hypertension. If patient has hypertension, it
must be medically controlled (< 150/90) prior to starting bevacizumab

- Proteinuria at screening

- Dementia or significantly altered mental status that would prohibit the understanding
and/or giving of informed consent

- Therapeutic anticoagulation is not by itself and exclusion criterion. However, for
certain high risk patients on therapeutic anticoagulation, eligibility will be
determined after discussion with the overall PI

- Any active bleeding

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

- Prior history of hypertensive crisis or hypertensive encephalopathy

- NYHA Grade II or greater congestive heart failure

- History of myocardial infarction or unstable angina within 6 months prior to Day 1

- History of stroke or transient ischemic attack within 6 months prior to day 1

- Significant vascular disease within 6 months prior to day 1

- History of hemoptysis within 1 month prior to day 1

- Presence of measurable lesion(s) by RECIST criteria with maximum diameter greater than
3 centimeters