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:

Recruiting

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 > 18 years old.

        Patients must have a Karnofsky performance status of > 60.

        Patients must have adequate bone marrow function (WBC > 3,000/microliter, ANC >
        1,500/mm^3, platelet count of > 100,000/mm^3, 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. 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: > 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 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 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.

        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 must not have active infection or serious intercurrent medical illness.

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

        Patients must not have any disease that will obscure toxicity or dangerously alter drug

        metabolism.

        Patients must not 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 on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the
        following criteria to be eligible:

        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 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).
      
Maximum Eligible Age:99 Years
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:

Secondary Outcome Measures

Measure:To evaluate response rates to this chemotherapy.
Time Frame:end of treatment
Safety Issue:
Description:
Measure:To evaluate overall survival in this population.
Time Frame:time of death
Safety Issue:
Description:
Measure:To evaluate toxicity profile of this combination.
Time Frame:completion of study
Safety Issue:
Description:
Measure: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) selfreporting tool.
Time Frame:completion of study
Safety Issue:
Description:

Details

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

Trial Keywords

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

Last Updated

April 20, 2017