First-Line Treatment of Bevacizumab, Carboplatin, and Paclitaxel in Treating Participants With Stage III-IV Ovarian, Primary Peritoneal, and Fallopian Tube Cancer
Condition: Fallopian Tube Carcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fallopian Tube Undifferentiated Carcinoma; FIGO Stage III Ovarian Cancer; FIGO Stage IIIA Ovarian Cancer; FIGO Stage IIIA1 Ovarian Cancer; FIGO Stage IIIA1(i) Ovarian Cancer; FIGO Stage IIIA1(ii) Ovarian Cancer; FIGO Stage IIIA2 Ovarian Cancer; FIGO Stage IIIB Ovarian Cancer; FIGO Stage IIIC Ovarian Cancer; FIGO Stage IVA Ovarian Cancer; FIGO Stage IVB Ovarian Cancer; Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Ovarian Undifferentiated Carcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Serous Adenocarcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Brenner Tumor
Intervention: Bevacizumab; Carboplatin; Paclitaxel
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well first-line treatment of bevacizumab, carboplatin, and
      paclitaxel work in treating participants with stage III- IV ovarian, primary peritoneal and
      fallopian tube cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the
      ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin
      and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      bevacizumab, carboplatin, and paclitaxel as first-line treatment may work better at treating
      ovarian, primary peritoneal, and fallopian tube cancer.
    

Eligibility criteria:

        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