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Study Summary
No. CERN09-02:.......Brain; Spinal......Mark R. Gilbert......Neuro Oncology
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Study Summary Title
Study Summary
Number:
CERN09-02
Study Title:Phase II trial of carboplatin and bevacizumab for the treatment of recurrent low-grade and anaplastic supratentorial, infratentorial and spinal cord ependymoma in adults
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Physician New Patient Referral
Name:Mark R. GilbertPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Neuro OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2883
Contact us about clinical trials
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General Information
Disease Group:Brain
Spinal
Supported By:CERN
Phase of Study:Phase IIReturn
Visit:
Treatment
Agents:
Bevacizumab
Carboplatin
Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
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.
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Study Objectives / Outcomes
Primary Objective:
    • To evaluate the efficacy of carboplatin and bevacizumab for the treatment of recurrent intracranial low grade or anaplastic ependymoma. The primary endpoint will be progression-free survival (PFS) at one year.

Secondary Objectives:
      • To evaluate response rates to this chemotherapy.
      • To evaluate overall survival in this population.
      • To evaluate toxicity profile of this combination.
      • To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT or MDASI-SP) self-reporting tool. This will include:
      • To evaluate longitudinal changes in symptom measures and determine the impact of the therapy on these parameters.
      • To measure symptom burden over the course of therapy to evaluate differences between patients individual symptom severity, overall mean symptom severity, and difference in scores on the interference items between responders and nonresponders.
      • To describe the variability of symptom severity longitudinally over the treatment course and follow-up period.

      Exploratory Objectives:
        • To evaluate safety and preliminary efficacy of this treatment in patients with recurrent spinal ependymomas.
        • To evaluate treatment effects of this combination on advanced MRI of the brain. Dr. Elizabeth Gerstner, Massachusetts General Hospital, will conduct this component of the research. The following parameters will be evaluated:
        • Diffusion weighted and diffusion tensor imaging
        • Perfusion MRI, for analysis of rCBV and Ktrans
        • Spectroscopy for CNI /metabolic lesion evaluation
        • To evaluate plasma levels of angiogenesis-related factors as predictors of outcomes. The following factors will be analyzed: vascular endothelial growth factor (VEGF), VEGFR-2, bFGF, PLGF, HGF, Tie-2, Interleukin 8, TIMP-1, E-selectin, ICAM and SDF1á. This component of the research will be performed by Dr. Martin Fleisher at MSKCC.
          • To evaluate paraffin embedded tissue samples (and frozen samples, if available) utilizing gene expression profiling (Illumina technology), immunohistochemistry and/or RT-PCR. Analysis will focus on expression of genes involved in angiogenesis and hypoxia-related tissue factors. This component of the research will be overseen by Dr. Keneth Aldape, at MD Anderson Cancer Center.
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        Study Status Information
        Study Activation / Registration Date:
        IRB Review and Approval Date:03/02/2011
        Study Type:Phase Ii Or Phase I/Ii
        Recruitment Status:Open
        Projected Accrual:46
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        Enrollment Eligibility
        If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

        Inclusion Criteria:1) Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth. The patient's histologic diagnosis must be confirmed on Central Pathology Review prior to registration Step 2. * If a patient has already had central pathology review at MDACC (for example, from a previous enrollment to protocol CERN08-02), the central pathology does not need to be repeated. Previous pathology confirmation can be utilized for this study's pathology eligibility testing.

        2) 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.

        3) 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 registered in the MDACC OMCR database prior to treatment with study drug.

        4) Patients must be >/= 18 years old.

        5) Patients must have a Karnofsky performance status of >/= 60.

        6) Patients must have adequate bone marrow function (WBC >/= 3,000/µl, ANC >/= 1,500/mm3, platelet count of >/= 100,000/mm3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGOT [AST <92.5 Units/L] and bilirubin </= 1.5 mg/dL), and adequate renal function (creatinine < 1.5 mg/dL and calculated creatinine clearance >/= 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.

        7) Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. If an MRI is being obtained to verify eligibility, it is recommended that the MRI parameters follow the specifications detailed in the protocol so that the patient will not require a repeat MRI prior to treatment start.

        8) At the time of registration: Patients must have recovered from the toxic effects of prior therapy: >/= 28 days from any investigational agent, >/= 28 days from prior cytotoxic therapy, >/= 14 days from vincristine, >/= 42 days from nitrosoureas, >/= 21 days from procarbazine administration, and >/= 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 Study Chair.

        9) Patients having undergone recent resection of recurrent or progressive tumor will be eligible with the following conditions apply: a) They have recovered from the effects of surgery. b) 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. c) 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 registration. If the within 96-hour after surgery scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

        10) 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.

        11) 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 PET or Thallium scanning, MR spectroscopy, or surgical/pathological documentation of disease.

        12) Women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to registration.

        13) Women of childbearing potential and male participants agree to practice adequate contraception.

        Exclusion Criteria:1) Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.

        2) Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.

        3) Patients must not have active infection or serious intercurrent medical illness.

        4) Patients must not be pregnant/breast feeding. Patients must not be pregnant because animal studies show that carboplatin and bevacizumab are teratogenic.

        5) Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

        6) Patients must not have received prior therapy with bevacizumab, or other agents known to target the Vascular Endothelial Growth Factor (VEGF) pathway including sorafenib, sunitinib, or cedirinib.

        7) Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg) despite antihypertensive medication.

        8) New York Heart Association (NYHA) Grade II or greater congestive heart failure.

        9) History of myocardial infarction or unstable angina within 12 months prior to Day 1.

        10) History of stroke or transient ischemic attack.

        11) Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.

        12) History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.

        13) Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). (To be eligible, Prothrombin time/international normalized ratio (PT INR) should be < 1.4 for patients not on warfarin.) Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria to be eligible: a) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices); b) 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.

        14) 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.

        15) Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.

        16) History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.

        17) Serious, non-healing wound, active ulcer, or untreated bone fracture.

        18) Proteinuria as demonstrated by a UPC ratio >/= 1.0 at screening, or Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).

        19) Known hypersensitivity to any component of bevacizumab.

        20) Patients must not have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).

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        Links
        Registration Number: NCT01295944
        Study Information on Clinical Trials Registry (clinicaltrials.gov)

        Other Links:
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        Results


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