Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Condition: Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Brenner Tumor
Intervention: Bevacizumab; Carboplatin; Laboratory Biomarker Analysis; Paclitaxel; Placebo; Quality-of-Life Assessment
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Given IV; Ancillary studies
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1873.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies carboplatin, paclitaxel, and bevacizumab to see how
      well they work compared to carboplatin, paclitaxel, and placebo in treating patients with
      stage III or stage IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. 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 or by stopping them from dividing.
      Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to
      grow and spread. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are
      more effective than carboplatin, paclitaxel, and placebo in treating ovarian epithelial,
      primary peritoneal, or fallopian tube cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary
             carcinoma or fallopian tube cancer; International Federation of Gynecology and
             Obstetrics (FIGO) stage III with any gross (macroscopic or palpable) residual disease
             or FIGO stage IV, defined surgically at the completion of initial abdominal surgery
             and with appropriate tissue available for histologic evaluation; the minimum surgery
             required was 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; if additional surgery was performed, it should have been in
             accordance with appropriate surgery for ovarian or peritoneal carcinoma described in
             the Gynecologic Oncology Group (GOG) Surgical Procedures Manual; however, the surgeon
             is not required to have performed all of the items contained in this section of the
             GOG Surgical Procedures Manual; 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;" measurable disease on post-operative imaging studies is
             not required for eligibility

          -  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
             carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified
             (N.O.S.); however, the histologic features of the tumor must be compatible with a
             primary Müllerian epithelial adenocarcinoma; if doubt exists, it is recommended that
             the investigator should have the slides reviewed by an independent pathologist or, if
             necessary, the Pathology Co-Chair, prior to entry; 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

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/µl equivalent to Common
             Toxicity Criteria for Adverse Events version (v)3.0 (CTCAE) grade 1; this ANC cannot
             have been induced or supported by granulocyte colony stimulating factors

          -  Platelets greater than or equal to 100,000/µl; (CTCAE grade 0-1)

          -  Creatinine =< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1

          -  Bilirubin less than or equal to 1.5 x ULN (CTCAE grade 1)

          -  Serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase less than or
             equal to 2.5 x ULN (CTCAE grade 1)

          -  Neuropathy (sensory and motor) less than or equal to CTCAE grade 1

          -  Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an
             in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic
             warfarin for management of venous thrombosis including pulmonary thrombo-embolus) and
             a partial thromboplastin time (PTT) < 1.2 times the upper limit of normal

          -  Patients with a GOG Performance Status of 0, 1, or 2

          -  Patients must be entered between 1 and 12 weeks after initial surgery performed for
             the combined purpose of diagnosis, staging and cytoreduction

          -  Patients with measurable and non-measurable disease are eligible; patients may or may
             not have cancer-related symptoms

          -  Patients who have met the pre-entry requirements

          -  An approved informed consent and authorization permitting release of personal health
             information must be signed by the patient or guardian

          -  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
             or prior to disease progression

        Exclusion Criteria:

          -  Patients with a current diagnosis of 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 (such as patients with
             stage Ia or Ib low grade epithelial ovarian or fallopian tube cancers) 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

          -  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

          -  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

          -  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

          -  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 I-B; 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

          -  With the exception of non-melanoma skin cancer 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

          -  Patients with acute hepatitis or active infection that requires parenteral antibiotics

          -  Patients with serious non-healing wound, ulcer, or bone fracture; this includes
             history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 28 days; patients with granulating incisions healing by secondary intention
             with no evidence of fascial dehiscence or infection are eligible but require weekly
             wound examinations

          -  Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
             vessels

          -  Patients with history or evidence upon physical examination of central nervous system
             (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

          -  Patients with clinically significant cardiovascular disease; this includes:

          -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg

          -  Myocardial infarction 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; this does not include 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 without permanent deficit)

          -  History of CVA within six months

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human or humanized antibodies

          -  Patients with clinically significant proteinuria; urine protein should be screened by
             urine protein-creatinine ratio (UPCR); 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]; 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); patients must have a UPCR < 1.0 to allow
             participation in the study

          -  Patients with or with anticipation of invasive procedures as defined below:

          -  Major surgical procedure, open biopsy or significant traumatic injury within 28 days
             prior to the first date of bevacizumab/placebo therapy (cycle 2)

          -  Major surgical procedure 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; please consult with the study chair
             prior to patient entry for any questions related to the classification of surgical
             procedures

          -  Core biopsy, within 7 days prior to the first date of bevacizumab/placebo therapy
             (cycle 2)

          -  Patients with GOG Performance Grade of 3 or 4

          -  Patients who are pregnant or nursing; 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

          -  Patients who have received prior therapy with any anti-vascular endothelial growth
             factor (VEGF) drug, including bevacizumab

          -  Patients with clinical symptoms or signs of gastrointestinal obstruction and who
             require parenteral hydration and/or nutrition

          -  Patients with medical history or conditions not otherwise previously specified which
             in the opinion of the investigator should exclude participation in this study; the
             investigator should feel free to consult the study chair or study co-chairs for
             uncertainty in this regard