Bevacizumab With or Without Everolimus in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Condition: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
MeSH terms: Carcinoma; Recurrence
Intervention: Bevacizumab; Everolimus; Laboratory Biomarker Analysis; Placebo
Intervention description: Given IV; Given PO; Correlative studies; Given PO
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Everolimus; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 150.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well bevacizumab with or without everolimus works
      in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube
      cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block
      tumor growth in different ways. Some block the ability of tumor cells to grow and spread.
      Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Bevacizumab and everolimus may also stop the growth of tumor cells by blocking blood
      flow to the tumor. It is not yet known whether bevacizumab is more effective when given
      together with or without everolimus in treating ovarian epithelial cancer, fallopian tube
      cancer, or primary peritoneal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
             primary peritoneal carcinoma; histologic documentation of the original primary tumor
             is required via the pathology report

          -  Patients must have measurable disease or detectable (non-measurable) disease:

               -  Measurable disease 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 greater than or equal to 10 mm when measured by computed
                  tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by
                  clinical exam; or greater than or equal to 20 mm when measured by chest x-ray;
                  lymph nodes must be greater than or equal to 15 mm in short axis when measured by
                  CT or MRI

               -  Detectable disease in a patient is defined as one who does not have measurable
                  disease but has at least one of the following conditions:

                    -  Baseline values of CA-125 at least 2 x upper limit of normal (ULN)

                    -  Ascites and/or pleural effusion attributed to tumor

                    -  Solid and/or cystic abnormalities on radiographic imaging that do not meet
                       RECIST 1.1 definitions for target lesions

          -  Patients in the measurable disease cohort must have at least one ?target lesion? to be
             used to assess response on this protocol as defined by RECIST 1.1; tumors within a
             previously irradiated field will be designated as ?non-target? lesions unless
             progression is documented or a biopsy is obtained to confirm persistence at least 90
             days following completion of radiation therapy

          -  Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
             protocol, if one exists; in general, this would refer to any active GOG phase III
             protocol or Rare Tumor Protocol for the same patient population

          -  Patients who have had one prior treatment must have a GOG performance status of 0, 1,
             or 2; patients who have had two or three prior treatments must have a GOG performance
             status of 0 or 1

          -  Patients should be free of active infection requiring parenteral antibiotics (with the
             exception of uncomplicated urinary tract infection [UTI])

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy

               -  Any hormonal therapy directed at the malignant tumor must be discontinued at
                  least one week prior to registration

               -  Any other prior therapy directed at the malignant tumor, including biological and
                  immunologic agents, must be discontinued at least 3 weeks prior to registration
                  (including small molecules and murine monoclonal antibodies); chimeric or human
                  or humanized monoclonal antibodies (including bevacizumab) or vascular
                  endothelial growth factor (VEGF) receptor fusion protein (including VEGF Trap,
                  aflibercept) must be discontinued for at least 12 weeks prior to registration; no
                  investigational therapy within 30 days prior to the first date of study treatment

          -  Prior therapy:

               -  Patients must have had one prior platinum-based chemotherapeutic regimen for
                  management of primary disease containing carboplatin, cisplatin, or another
                  organoplatinum compound' this initial treatment may have included intraperitoneal
                  therapy, consolidation, non-cytotoxic agents or extended therapy administered
                  after surgical or non-surgical assessment

               -  Patients are allowed to receive, but are not required to receive, two additional
                  cytotoxic regimens for management of recurrent or persistent disease, with no
                  more than 1 non-platinum, non-taxane regimen

               -  Patients are allowed to receive, but are not required to receive, biologic
                  (non-cytotoxic) therapy as part of their primary treatment regimen; patients must
                  have NOT received any non-cytotoxic therapy for management of recurrent or
                  persistent disease

               -  Patients who have received only one prior cytotoxic regimen (platinum-based
                  regimen for management of primary disease), must have a platinum-free interval of
                  less than 12 months, or have progressed during platinum-based therapy, or have
                  persistent disease after a platinum-based therapy

               -  For the purposes of this study, poly (adenosine diphosphate [ADP]-ribose)
                  polymerase (PARP) inhibitors will be considered ?cytotoxic,? and prior treatment
                  with PARP inhibitors for primary or recurrent disease WILL be allowed (either
                  alone or in combination with chemotherapy)

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

          -  Platelets greater than or equal to 100,000/mcl

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

          -  Bilirubin less than or equal to 1.5 x ULN

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less
             than or equal to 3 x ULN

          -  Alkaline phosphatase less than or equal to 2.5 x ULN

          -  Prothrombin time (PT) such that international normalized ratio (INR) is less than or
             equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a
             stable dose of therapeutic warfarin for management of deep vein thrombosis including
             pulmonary embolism)

          -  Partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of
             normal

          -  Fasting serum cholesterol less than or equal to 300 mg/dL OR less than or equal to
             7.75 mmol/L AND

          -  Fasting triglycerides less than or equal to 300 mg/dL or 3.42 mmol/L

          -  Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection
             of 24-hour urine measurement of urine protein is recommended; UPC ratio of spot urine
             is an estimation of the 24-hour urine protein excretion?a UPC ratio of 1 is roughly
             equivalent to a 24-hour urine protein of 1 gm

          -  Patients of childbearing potential must have a negative serum pregnancy test prior to
             the study entry and be practicing an effective form of contraception

          -  Patients must have signed an approved informed consent and authorization permitting
             the release of personal health information

          -  Patients must meet pre-entry requirements

          -  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 within 6 months prior to registration

               -  New York Heart Association (NYHA) class II or greater congestive heart failure

               -  Serious cardiac arrhythmia requiring medication; this does not include
                  asymptomatic, atrial fibrillation with controlled ventricular rate

               -  Patients who have received prior treatment with an anthracycline (including
                  doxorubicin and or liposomal doxorubicin) and have an ejection fraction < 50%

               -  Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
                  peripheral vascular disease (at least brief [< 24 hours (hrs)] episodes of
                  ischemia managed non-surgically and without permanent deficit)

        Exclusion Criteria:

          -  Patients who have received prior everolimus or any other mammalian target of rapamycin
             (mTOR) inhibitor

          -  Patients with other invasive malignancies, with the exception of non-melanoma skin
             cancer and other specific malignancies, are excluded if there is any evidence of other
             malignancy being present within the last three years; patients are also excluded if
             their previous cancer treatment contraindicates this protocol therapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of ovarian, fallopian tube or primary
             peritoneal cancer within the last three years 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 OTHER
             THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within
             the last three years 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 the patient remains free of recurrent or
             metastatic disease

          -  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 prior to the first date of study treatment

          -  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
             prior to the first date of study treatment

          -  Known hypersensitivity to murine or chimeric antibodies

          -  Major surgery within 28 days prior to the first date of study treatment

          -  Patients with clinical symptoms or signs of gastrointestinal obstruction and patients
             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 can consult the Study Chair or Study Co-Chairs for uncertainty in this
             regard

          -  Patients who are pregnant or nursing

          -  Patients with active hepatitis B or C

               -  Laboratory confirmation to exclude hepatitis B and C is required in any patient
                  considered at high risk for hepatitis B or C; risk factors can include:

                    -  You currently live in (or have lived in) Asia, Africa, Central and South
                       America, Eastern Europe, Spain, Portugal, and Greece

                    -  Known or suspected past hepatitis B infection

                    -  Known or suspected past hepatitis C infection (including past interferon
                       ?curative? treatment)

                    -  Blood transfusion(s) prior to 1990

                    -  Current or prior IV drug use

                    -  Current or prior dialysis

                    -  Household contact with hepatitis B or hepatitis C infected person(s)

                    -  Current or prior high-risk sexual activity

                    -  Body piercing or tattoos

                    -  Mother known to have hepatitis B

                    -  History suggestive of hepatitis B infection, e.g., dark urine, jaundice,
                       right upper quadrant pain