Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Condition: Clear Cell Adenocarcinoma; 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; Mucinous Adenocarcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Ovarian Undifferentiated Carcinoma; Primary Peritoneal Clear Cell Adenocarcinoma; Primary Peritoneal Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Primary Peritoneal Transitional Cell Carcinoma; Primary Peritoneal Undifferentiated Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Fallopian Tube Neoplasms; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Brenner Tumor; Recurrence
Intervention: Bevacizumab; Carboplatin; Docetaxel; Gemcitabine Hydrochloride; Laboratory Biomarker Analysis; Paclitaxel; Quality-of-Life Assessment
Intervention description: Given IV; Given IV; Given IV; Given IV; Correlative studies; Given IV; Ancillary studies
Intervention MeSH terms: Paclitaxel; Docetaxel; Bevacizumab; Carboplatin; Gemcitabine; 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: None (Open Label)
Enrollment: 1052.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies carboplatin, paclitaxel and gemcitabine hydrochloride
      when given together with or without bevacizumab after surgery to see how well it works in
      treating patients with ovarian, epithelial, primary peritoneal, or fallopian tube cancer that
      has come back. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine
      hydrochloride 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. Immunotherapy with
      monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet
      known whether combination chemotherapy is more effective when given with or without
      bevacizumab after surgery in treating patients with ovarian, epithelial, primary peritoneal,
      or fallopian tube cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients enrolled after August 28, 2011 must be candidates for cytoreductive surgery
             and consent to have their surgical treatment determined by randomization

          -  Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal
             primary or fallopian tube carcinoma, which is now recurrent

          -  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.)

          -  Patients must have had a complete response to front-line platinum-taxane therapy (at
             least three cycles)

          -  A complete response to front-line chemotherapy must include: negative physical exam,
             negative pelvic exam and normalization of CA125, if elevated at baseline; although not
             required, any radiographic assessment of disease status (e.g. CT, magnetic resonance
             imaging [MRI], positron emission tomography [PET]/CT, etc) obtained following the
             completion of primary therapy should be considered negative for disease

          -  All patients must have also had a treatment-free interval without clinical evidence of
             progressive disease of at least 6 months from completion of front-line chemotherapy
             (both platinum and taxane); front-line therapy may have included a biologic agent
             (i.e. bevacizumab)

          -  Front-line treatment may include maintenance therapy following complete clinical or
             pathological response; however, maintenance cytotoxic chemotherapy must be
             discontinued for a minimum of 6 months prior to documentation of recurrent disease;
             patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE
             provided their recurrence is documented more than 6 months from primary cytotoxic
             chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has
             elapsed since their last infusion of biological therapy

          -  Patients must have clinically evident recurrent disease for the purpose of this study

          -  Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST]) is defined
             as at least one lesion that can be accurately measured in at least one dimension
             (longest dimension to be recorded); each lesion must be more than or equal to 20 mm
             when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm
             when measured by spiral CT

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to
             Common Toxicity Criteria for Adverse Events version (v)4.0 (CTCAE) grade 1

          -  Platelets greater than or equal to 100,000/mm^3 (CTCAE grade 0-1)

          -  Creatinine (non-isotope dilution mass spectrometry [IDMS]) =< 1.5 x institutional
             upper limit normal (ULN), CTCAE grade 1

          -  Total bilirubin =< 1.5 ULN (CTCAE grade 1)

          -  Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) =< 2.5
             times the upper limit of normal in the absence of liver metastasis; SGOT/AST < 5.0
             times ULN in the presence of liver metastasis

          -  Alkaline phosphatase =< 2.5 times the upper limit of normal in the absence of liver
             metastasis; alkaline phosphatase < 5.0 times ULN in the presence of liver metastasis

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients must have a urine
             protein-to-creatinine ratio (UPCR) < 1.0 mg/dL

          -  This eligibility criterion does not apply to patients enrolled after August 28, 2011;
             patients who are not candidates for surgical cytoreduction are eligible for the
             chemotherapy randomization; patients are not considered candidates for surgical
             cytoreduction if complete cytoreduction in the estimation of the investigator is
             impossible or a medical infirmity precludes exploration and debulking

          -  Patients must have met the pre-entry requirements as specified

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

        Exclusion Criteria:

          -  Patients who have received more than one previous regimen of chemotherapy (maintenance
             is not considered a second regimen)

          -  Patients receiving concurrent immunotherapy, or radiotherapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis are excluded

          -  Patients whom have already undergone secondary cytoreduction for recurrent disease are
             excluded

          -  Patients with a prior histologic diagnosis of borderline, low malignant potential
             (grade 0) epithelial carcinoma that was surgically resected and who subsequently
             developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer
             are eligible provided that they meet the criteria listed above

          -  Patients who require parenteral hydration or nutrition and have evidence of partial
             bowel obstruction or perforation

          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other
             than ovarian, fallopian tube, and primary peritoneal) are excluded

          -  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 International Federation of Gynecology and Obstetrics
             (FIGO) grade 3 lesions

          -  Patients with uncontrolled infection

          -  Patients with concurrent severe medical problems unrelated to the malignancy that
             would significantly limit full compliance with the study or expose the patient to
             extreme risk or decreased life expectancy

          -  Patients with >= grade 2 peripheral neuropathy

          -  Patients with a history of allergic reactions to carboplatin and/or paclitaxel or
             chemically similar compounds; patients with allergic (hypersensitivity) reactions to
             these chemotherapeutic agents are NOT excluded IF they were successfully retreated
             following a desensitization program or protocol

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients with known
             hypersensitivity to Chinese hamster ovary cell products or other recombinant human or
             humanized antibodies

          -  Patients of childbearing potential, not practicing adequate contraception, patients
             who are pregnant or patients who are nursing are not eligible for this trial; to date,
             no fetal studies in animal or humans have been performed; the possibility of harm to a
             fetus is likely; bevacizumab specifically inhibits VEGF, which is responsible for the
             formation of new blood vessels during development, and antibodies can cross the
             placenta; therefore, bevacizumab should not be administered to pregnant women; in
             addition, there are unknown immediate and long-term consequences of chemotherapy
             administration to these women; in addition, surgical exploration as mandated by
             randomization during pregnancy may cause imminent mortal consequences; further, 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;
             subjects will be apprised of the large potential risk to a developing fetus

          -  Patients with other invasive malignancies, with the exception of non-melanoma skin
             cancer, who had (or have) any evidence of the other cancer present within the last 5
             years or whose previous cancer treatment contraindicates this protocol therapy

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients with active
             bleeding or pathologic conditions that carry high risk of bleeding such as a known
             bleeding disorder, coagulopathy, or tumor involving major vessels

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients with a 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 a history of stroke within 5 years of the first date of treatment on
             this study

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients with clinically
             significant cardiovascular disease; this includes:

               -  Patients with significant cardiac conduction abnormalities, i.e. PR interval >
                  0.24 seconds (sec) or 2nd or 3rd degree atrioventricular (AV) block

               -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
                  Hg

               -  Myocardial infarction, cardiac arrhythmia 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

               -  Grade II or greater peripheral vascular disease (exception: episodes of ischemia
                  < 24 hours [hrs] in duration, that are managed non-surgically and without
                  permanent deficit)

               -  History of cerebrovascular attack (CVA) within six months

          -  This criterion applies only to the patients enrolled before August 29, 2011 and those
             enrolled after this date electing to receive bevacizumab; patients who have had a
             major surgical procedure, open biopsy, dental extractions or other dental
             surgery/procedure that results in an open wound, or significant traumatic injury
             within 28 days prior to the first date of treatment on this study, or anticipation of
             need for major surgical procedure during the course of the study; patients with
             placement of vascular access device or core biopsy within 7 days prior to the first
             date of treatment on this study

          -  Patients undergoing pre-treatment secondary cytoreduction will undergo therapy with
             bevacizumab on cycle #2

          -  Patients undergoing pre-treatment surgery for purposes other than cytoreduction may
             also participate provided they meet eligibility; patients randomized to arms
             containing bevacizumab must wait a minimum of 28 days since that procedure to begin
             protocol treatment; patients who undergo an uncomplicated port placement must wait a
             minimum of 7 days to begin protocol treatment