| Eligibility |
Inclusion Criteria:
1. Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary
carcinoma or fallopian tube cancer; FIGO stage III and IV defined surgically at the
completion of initial abdominal surgery and with appropriate tissue available for
histologic evaluation. The minimum surgery required is an abdominal surgery providing
tissue for histologic evaluation and establishing and documenting the primary site and
stage, as well as a maximal effort at tumor debulking.
2. (continued from no. 1) Those patients with stage III cancer in which the largest
maximal diameter of any residual tumor implant at the completion of this initial
surgery is no greater than 1 cm will be defined as optimal; all others will be defined
as suboptimal.
3. The histologic features of the tumor must be compatible with a primary Müllerian
epithelial adenocarcinoma. Patients with the following histologic epithelial cell
types are eligible: Serous adenocarcinoma, Endometrioid adenocarcinoma, Mucinous
adenocarcinoma, Undifferentiated carcinoma, Clear cell adenocarcinoma, Mixed
epithelial carcinoma, Transitional cell, Malignant Brenner's Tumor, Adenocarcinoma
N.O.S. Patients may have co-existing fallopian tube carcinoma in-situ so long as the
primary origin of invasive tumor is ovarian, peritoneal or fallopian tube.
4. Patients must be entered no later than 12 weeks after initial surgery performed for
the combined purpose of diagnosis, staging and cytoreduction.
5. Patients with measurable and non-measurable disease are eligible. Patients may or may
not have cancer-related symptoms.
6. Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy
as indicated at the lowest effective dose(s) for control of menopausal symptoms at any
time, but not progestins for management of anorexia while on protocol directed
therapy.
7. Patients with an ECOG Performance Status of 0, 1, or 2.
8. Patients must have normal organ and marrow function as defined below: leukocytes
>3,000/mcL; absolute neutrophil count >1,500/mcL; platelets >100,000/mcL; total
bilirubin <1.5 X institutional upper limits of normal; AST(SGOT)/ALT(SGPT) <2.5 X
institutional upper limit of normal; Alkaline phosphatase (AP) <2.5 X institutional
upper limit of normal; creatinine <1.5X institutional upper limit of normal OR
creatinine clearance >50 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal
9. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. Patients with borderline epithelial ovarian tumor (formerly "tumors of low malignant
potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian
tube cancer treated with surgery only are not eligible. Patients with a prior
diagnosis of a borderline tumor that was surgically resected and who subsequently
develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian
tube cancer are eligible, provided that they have not received prior chemotherapy for
any ovarian tumor.
2. Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded. Prior radiation for localized cancer of the breast, head and
neck, or skin is permitted, provided that it was completed more than three years prior
to registration, and the patient remains free of recurrent or metastatic disease.
3. Patients who have received prior chemotherapy for any abdominal or pelvic tumor
including neo-adjuvant chemotherapy for their ovarian, primary peritoneal or fallopian
tube cancer are excluded. Patients may have received prior adjuvant chemotherapy for
localized breast cancer, provided that it was completed more than three years prior to
registration, and that the patient remains free of recurrent or metastatic disease.
4. Patients who have received any targeted therapy (including but not limited to
vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management
of their epithelial ovarian or peritoneal primary cancer.
5. Patients who are currently participating or planning to participate in an experimental
drug study other than a Genentech-sponsored bevacizumab cancer study or who are
receiving other investigational agents.
6. Patients with synchronous primary endometrial cancer, or a past history of primary
endometrial cancer, are excluded, unless all of the following conditions are met:
Stage not greater than IB; no more than superficial myometrial invasion, without
vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary
serous, clear cell or other FIGO Grade 3 lesions.
7. With the exception of superficial basal cell and superficial squamous (skin) cell,
carcinoma in situ of the cervix and other specific malignancies as noted above,
patients with other invasive malignancies who had (or have) any evidence of the other
cancer present within the last five years or whose previous cancer treatment
contraindicates this protocol therapy are excluded.
8. Patients with acute hepatitis or active infection that requires parenteral
antibiotics.
9. Patients with serious non-healing wound, ulcer, or untreated bone fracture. This
includes a history of abdominal fistula or gastrointestinal perforation within 6
months prior to Day 1. Patients with granulating incisions healing by secondary
intention with no evidence of fascial dehiscence or infection are eligible but require
weekly wound examinations until closure.
10. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy (in the absence of therapeutic
anticoagulation), or tumor involving major vessels.
11. History of hemoptysis (>/=1/2 teaspoon of bright red blood per episode) within 1 month
prior to Day 1.
12. Patients with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic
attack (TIA) or subarachnoid hemorrhage within six months of the first date of
treatment on this study.
13. Patients with clinically significant cardiovascular disease. This includes: 1)
Uncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm Hg; 2)
Myocardial infarction or unstable angina < 6 months prior to registration; 3) New York
Heart Association (NYHA) Grade II or greater congestive heart failure; 4) Serious
cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial
fibrillation with controlled ventricular rate
14. (continued from no. 13) CTCAE Grade 2 or greater peripheral vascular disease (at least
brief (<24 hrs) episodes of ischemia managed non-surgically and without permanent
deficit); Prior history of hypertensive crisis or hypertensive encephalopathy;
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Day 1
15. Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human or humanized antibodies
16. Patients with known hypersensitivity to any component of bevacizumab
17. Patients with clinically significant proteinuria at screening as demonstrated by urine
protein:creatinine (UPCR) ratio >/= 1.0 at screening. The UPCR has been found to
correlate directly with the amount of protein excreted in a 24 hour urine collection.
Specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hour urine
collection. Obtain at least 4 ml of a random urine sample in a sterile container (does
not have to be a 24 hour urine). Send sample to lab with request for urine protein and
creatinine levels [separate requests].
18. (continued from no. 17) The lab will measure protein concentration (mg/dL) and
creatinine concentration (mg/dL). The UPCR is derived as follows: protein
concentration (mg/dL)/creatinine (mg/dL).
19. Patients with or with anticipation of invasive procedures as defined below: Major
surgical procedure within 28 days of initiating bevacizumab or major procedures
anticipated during the course of the study. This includes, but is not limited to
abdominal surgery (laparotomy or laparoscopy) prior to disease progression, such as
colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or
second look surgery.
20. (continued from no. 19) Core biopsy or other minor surgical procedure, excluding
placement of a vascular access device, within 7 days prior to the first date of
bevacizumab therapy
21. Patients with ECOG Performance Grade of 3 or 4
22. Patients who are pregnant (positive pregnancy test) or nursing. Use of effective means
of contraception (men and women) in subjects of child-bearing potential. To date, no
fetal studies in animals or humans have been performed. The possibility of harm to a
fetus is likely. Bevacizumab specifically inhibits VEGF, which is responsible for
formation of new blood vessels during development, and antibodies can cross the
placenta. Therefore, bevacizumab should not be administered to pregnant women.
23. (continued from no. 22) Subjects will be apprised of the large potential risk to a
developing fetus. It is not known whether bevacizumab is excreted in human milk.
Because many drugs are excreted in human milk, bevacizumab should not be administered
to nursing women. Patients of childbearing potential must agree to use contraceptive
measures during study therapy and for at least six months after completion of
bevacizumab therapy.
24. Patients under the age of 18.
25. Patients who have received prior therapy with any anti-VEGF drug, including
bevacizumab.
26. Patients with clinical symptoms or signs of gastrointestinal obstruction and who
require parenteral hydration and/or nutrition.
27. Patients with medical history or conditions not otherwise previously specified which
in the opinion of the investigator should exclude participation in this study.
28. Uncontrolled intercurrent illness including, but not limited to, 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.
29. Known HIV-positive patients on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with bevacizumab. In
addition, these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.
30. Inability to comply with study and/or follow-up procedures
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