Clinical Trials /

Carboplatin and Bevacizumab for Recurrent Ependymoma

NCT01295944

Description:

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

Related Conditions:
  • Anaplastic Ependymoma
  • Ependymoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carboplatin and Bevacizumab for Recurrent Ependymoma
  • Official 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: A Multi-Center Trial

Clinical Trial IDs

  • ORG STUDY ID: 160009
  • SECONDARY ID: 16-C-0009
  • NCT ID: NCT01295944

Conditions

  • Ependymoma
  • Anaplastic Ependymoma

Interventions

DrugSynonymsArms
Carboplatin1
Bevacizumab1

Purpose

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

Detailed Description

      Background:

        -  Ependymomas are glial based tumors arising from the ependymal lining of the ventricular
           system and central canal of the spinal cord

        -  These tumors affect both adults and children and represent approximately 1.2%-7.8% of
           all intracranial cancers.

        -  Currently, the standard therapy for newly diagnosed low-grade ependymoma includes total
           surgical excision, when possible, followed by radiation therapy. Complete surgical
           resection is often not possible because of the location of the tumor and the concern for
           damage to surrounding eloquent brain during surgery. The situation is even more critical
           for patients with anaplastic ependymomas because of the higher proliferative rate and
           greater propensity for tumor infiltration into surrounding normal brain, preventing any
           possibility of complete tumor removal by surgery.

        -  For patients with the more aggressive anaplastic ependymoma, chemotherapy is often
           administered either before or after the radiation in the hope that infiltrating tumor
           cells will be eliminated.

        -  Extensive experience has been gathered with the use of bevacizumab in other
           neuroepithelial tumors such as malignant gliomas. Based on the interesting results
           observed in the reported small series of patients with recurrent ependymomas treated
           with bevacizumab, as well as on the evidence of VEGF-promoted angiogenesis in these
           tumors, we designed a phase II study to test the efficacy of bevacizumab in patients
           with recurrent ependymoma. As results in most types of tumors have indicated that
           anti-angiogenesis therapies are more effective when given in combination with cytotoxic
           chemotherapy, in this study bevacizumab will be combined with carboplatin. The choice of
           carboplatin is justified by the fact that, as detailed above, this remains the most
           effective agent in this disease, and extensive toxicity data is available for the
           combination of bevacizumab and carboplatin in a variety of tumor types, including GBMs.

      Objective:

      To evaluate the efficacy of carboplatin and bevacizumab for the treatment of recurrent low
      grade or anaplastic ependymoma. The primary endpoint will be progression-free survival (PFS)
      at one year.

      Eligibility:

        -  Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There
           must be pathologic or imaging confirmation of tumor progression or regrowth.

        -  Patients must be greater than or equal to18 years old.

        -  Patients must have a Karnofsky performance status of greater than or equal to 60.

        -  Patients must have adequate bone marrow function, adequate liver function and adequate
           renal function before starting therapy.

        -  Patients must have recovered from the toxic effects of prior therapy.

        -  Patients having undergone recent resection of recurrent or progressive tumor will be
           eligible.

        -  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.

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

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

        -  Patients must not have any significant medical illnesses or active infection.

        -  Patients must not have history of any other cancer.

        -  Patients must not be pregnant/breast feeding.

        -  Patients must not have received prior therapy with bevacizumab, or related drugs.

        -  No active bleeding or pathological condition that carries a high risk of bleeding.

        -  No major surgical procedure, open biopsy, or significant traumatic injury within 28
           days.

      Design:

        -  This is a phase II study to evaluate the efficacy of carboplatin and bevacizumab for the
           treatment of recurrent low grade or anaplastic ependymoma. This trial is designed
           utilizing a Simon optimal two-stage design.

        -  Carboplatin will be given on day 1 of each cycle. Bevacizumab will be administered on
           days 1 and 15 of each cycle. The total duration of treatment will be 6 cycles. After
           cycle 6, carboplatin should be discontinued, but bevacizumab may be continued at the
           discretion of the treating physician.

        -  Patients will be monitored for hematologic or serologic evidence of myelosuppression,
           hepatic injury, renal injury, and electrolyte disturbances and for clinical evidence of
           other toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalThe total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizubab may be continued at the descretion of the treating physician.
  • Carboplatin
  • Bevacizumab

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 (WBC greater than or equal to
        3,000/microliter, 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 (SGOT [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 MRI or
        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 PET or Thallium scanning, MR spectroscopy, or
        surgical/pathological documentation of disease.

        Women of childbearing potential must have a negative B-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 withany 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.

        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 mmHg and/or
        diastolic blood pressure > 100 mmHg) despite antihypertensive medication.

        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.

        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 (PT INR)
        should be < 1.4 for patients not on warfarin.)

        Patients receiving full-dose anticoagulants therapy (e.g., warfarin or 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 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival (PFS) at one year
Time Frame:one year after end of treatment
Safety Issue:
Description:Proportion of patients that have progressive disease after 1 year

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Chemotherapy
  • Brain Tumor
  • Spinal Cord Tumor
  • Malignancy
  • Neurologic

Last Updated

May 18, 2021