| Exclusion Criteria: | 1) Patients w/concurrent diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive eipthelial ovarian, primary peritoneal, or fallopian tube cancer treated w/surgery only (such as those with stage IA or IB low grade EO or FT cancers) are not eligible. Patients w/prior diagnosis of a borderline tumor that was surgically resected & who subsequently develop an unrelated, new invasive eipthelial ovarian, primary peritoneal, 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 chemotherap for localized breast cancer, provided that is 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, primary peritoneal or fallopian tube carcinoma.
5) 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 1B; 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.
6) With the exception of non-melanoma skin cancer and other specific malignancies as noted above, patients with other invasive malignancies who had (or have) an evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy are excluded.
7) Patients with acute hepatitis or active infection that requires parenteral antibiotics.
8) Patients with serious, non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess with 28 days. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examination.
9) Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
10) Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controleld with standard medical therapy, any brain metastases, of history of cerebrovasculaf accident (CVA, stroke), transient ischemic attack (TIA) or subarrachnoid hemmorrhage within six months of the first date of treatment on this study.
11) Pts w/clinically significant cardiovascular disease including: uncontrolled hypertension, defined as systolic >150 mm Hg or diastolic >90 mm Hg; MI or unstable angina <6 months prior to registration; New York Heart Association (NYHA) Grade II or greater congestive heart failure; Serious cardiac arrhythmia requiring medication NOT including asymptomatic, atrial fibrillation with controlled ventricular rate. CTCAE Grade 2 or greater peripheral vascular disease (at least brief (<24 hrs) episodes of ischemia managed non-surgically and w/o permanent deficit; history of CVA within six months.
12) Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
13) Patients w/clinically significant proteinuria. Urine protein should be screened by urine protein-creatinine ratio (UPCR). A UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hr urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hr urine). Send sample to lab with separate requests for urine protein & creatinine levels. Lab will measure protein concentration (mg/dL) & creatinine concentration (mg/dL). The UPCR = protein concentration (mg/dL)/creatinine (mg/dL). Patients must have a UPCR <1.0 to allow participation in the study.
14) Patients with anticipation of invasive procedures prior to the course of the study: Major surgical procedure, open biopsy or significant traumatic injury w/in 28 days prior to 1st date of bevacizumab/placebo therapy (cycle 2); Core biopsy within 7 days prior to the first date of bevacizumab/placebo therapy (cycle 2).
15) Patients with anticipation of major surgical procedure during the course of the study including but not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression, (i.e. colostomy or enterostomy reversal, interval or secondary cytoreductive surgery or second look surgery). Consult Study Chair prior to pt entry if questions re classification of surgical procedures.
16) Patients with GOG Performance Grade of 3 or 4.
17) Pts who are pregnant or nursing. Bevacizumab specifically inhibits VEGF, which is responsible for formation of new blood vessels during development; antibodies can cross the placenta. Bevacizumab should not be administered to pregnant women due to the possibility of harm to the fetus. Subjects will be apprised of this large potential risk. It is unknown whether bevacizumab is excreted in human milk & should not be administered to nursing women. Pts of childbearing potential must agree to use contraceptive measures during study therapy & for at least 6 months after completion of therapy.
18) Patients under the age of 18.
19) Patients who have received prior therapy with any anti-VEGF drug, including bevacizumab.
20) Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.
21) Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in the study. The investigator should feel free to consult the Study Chair or Co-Chairs for uncertainty in this regard. |