Carboplatin and Bevacizumab for Recurrent Ependymoma
Condition: Ependymoma; Anaplastic Ependymoma
MeSH terms: Ependymoma
Intervention: Carboplatin; Bevacizumab
Intervention description: Carboplatin will be given on day 1 of each cycle; the carboplatin dose should be calculated using the Calvert formula: Carboplatin dose (mg) = target Area Under the Curve (AUC) x (Creatinine clearance (CrCl) + 25; The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued.; Bevacizumab will be administered on days 1 and 15 of each cycle. Bevacizumab will be administered at a dose of 10 mg/kg; The total duration of treatment will be 6 cycles. After cycle 6, bevacizumab may be continued at the discretion of the treating physician.
Intervention MeSH terms: Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chemotherapy; Brain Tumor; Spinal Cord Tumor; Malignancy; Neurologic

Summary:

      The goal of this clinical research study is to learn if the combination of bevacizumab and
      carboplatin can help to control recurrent ependymoma. The safety of this drug combination
      will also be studied.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma.
             There must be pathologic or imaging confirmation of tumor progression or regrowth.

          -  The patient must have at least 1 block of tissue or 15 unstained slides at a minimum
             available for central pathology review and molecular profiling of the tissue sample.

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study. Patients must have signed an authorization for
             the release of their protected health information.

          -  Patients must be greater than or equal to 18 years old.

          -  Patients must have a Karnofsky performance status of > 60.

          -  Patients must have adequate bone marrow function (white blood cell (WBC) greater than
             or equal to 3,000/microliter, absolute neutrophil count (ANC) greater than or equal to
             1,500/mm^3, platelet count of greater than to equal to 100,000/mm^3, and hemoglobin
             greater than or equal to 10 gm/dl), adequate liver function (Serum glutamic
             oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST) <92.5 Units/L] and
             bilirubin less than or equal to 1.5 mg/dL), and adequate renal function (creatinine <
             1.5 mg/dL and calculated creatinine clearance greater than or equal to 60 cc/min)
             before starting therapy. Eligibility level for hemoglobin may be reached by
             transfusion.

          -  Patients must have shown unequivocal radiographic evidence for tumor progression by
             magnetic resonance imaging (MRI) or computed tomography (CT) scan.

          -  At the time of registration: Patients must have recovered from the toxic effects of
             prior therapy: greater than or equal to 28 days from any investigational agent,
             greater than or equal to 28 days from prior cytotoxic therapy, greater than or equal
             to 14 days from vincristine, greater than or equal to 42 days from nitrosoureas,
             greater than or equal to 21 days from procarbazine administration, and greater than or
             equal to 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide,
             cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the
             definition of non-cytotoxic agents should be directed to the Principal Investigator.

          -  Patients having undergone recent resection of recurrent or progressive tumor will be
             eligible as long as all of the following conditions apply:

          -  They have recovered from the effects of surgery.

          -  A minimum of 28 days have elapsed from the day of surgery to the day of registration
             Step 2.

          -  For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration
             Step 2.

          -  Residual disease following resection of recurrent ependymoma is not mandated for
             eligibility into the study. To best assess the extent of residual disease
             post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate
             post-operative period or at least 4 weeks post-operatively, within 14 days prior to
             consent. If the within 96-hour after surgery scan is more than 14 days before consent
             the scan needs to be repeated. If the steroid dose is increased between the date of
             imaging and consent, a new baseline MRI/CT is required on a stable steroid dosage for
             at least 5 days.

          -  Patients must have failed prior radiation therapy* and must have an interval of
             greater than or equal to 42 days from the completion of radiation therapy to study
             entry. Note: Patients with an indication for craniospinal radiotherapy (i.e.,
             extensive leptomeningeal disease) but have refused palliative craniospinal
             radiotherapy are eligible.

          -  Patients with prior therapy that included interstitial brachytherapy or stereotactic
             radiosurgery must have confirmation of true progressive disease rather than radiation
             necrosis based upon either positron emission tomography (PET) or Thallium scanning, MR
             spectroscopy, or surgical/pathological documentation of disease.

          -  Women of childbearing potential must have a negative B (Beta)-human chorionic
             gonadotropin (HCG) pregnancy test documented within 14 days prior to registration.

          -  Women of childbearing potential and male participants agree to practice adequate
             contraception.

        EXCLUSION CRITERIA:

          -  Patients with any significant medical illnesses that in the investigators opinion
             cannot be adequately controlled with appropriate therapy or would compromise the
             patients ability to tolerate this therapy.

          -  Patients with a history of any other cancer (except non-melanoma skin cancer or
             carcinoma insitu of the cervix), unless in complete remission and off of all therapy
             for that disease for a minimum of 3 years are ineligible.

          -  Patients with an active infection or serious intercurrent medical illness.

          -  Patients found to be pregnant/breast feeding. Patients must not be pregnant because
             animal studies show that carboplatin and bevacizumab are teratogenic

          -  Patients with any disease that will obscure toxicity or dangerously alter drug
             metabolism.

          -  Patients who have received prior therapy with bevacizumab, or related drugs (previous
             therapy with carboplatin is allowed).

          -  Inadequately controlled hypertension (defined as systolic blood pressure >150
             millimeters of mercury (mmHg) and/or diastolic blood pressure > 100 mmHg) despite
             antihypertensive medication.

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure.

          -  History of myocardial infarction or unstable angina within 12 months prior to Day 1.

          -  History of stroke or transient ischemic attack.

          -  Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Day 1.

          -  History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per
             episode) within 1 month prior to Day 1.

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation). (To be eligible, Prothrombin time/international
             normalized ratio (prothrombin time (PT) international normalized ratio (INR)) should
             be < 1.4 for patients not on warfarin.)

          -  Patients receiving full-dose anticoagulants therapy (e.g., warfarin or
             Low-molecular-weigh (LMW) heparin) and does not meet both of the following criteria:

          -  No active bleeding or pathological condition that carries a high risk of bleeding
             (e.g., tumor involving major vessels or known varices).

          -  In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a
             stable dose of low molecular weight heparin.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1 of treatment or anticipation of need for major surgical procedure
             during the course of the study.

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to Day 1.

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             Day 1.

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture.

          -  Proteinuria as demonstrated by a urine protein:creatinine (UPC) ratio greater than or
             equal to 1.0 at screening, or Urine dipstick for proteinuria greater than or equal to
             2+ (patients discovered to have greater than or equal to 2+ proteinuria on dipstick
             urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate
             less than or equal to 1g of protein in 24 hours to be eligible).

          -  Known hypersensitivity to any component of bevacizumab.

          -  Patients has current active hepatic or biliary disease (with exception of patients
             with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per
             investigator assessment).