Clinical Trials /

Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

NCT01884740

Description:

Central nervous system (CNS) malignancies are the second most common malignancy and the most common solid tumor of childhood, including adolescence. Annually in the United States, approximately 2,200 children are diagnosed with CNS malignancy and rates appear to be increasing. CNS tumors are the leading cause of death from solid tumors in children. Survival duration after diagnosis in children is highly variable depending in part on age at diagnosis, location of tumor, and extent of resection; however, most children with high grade glioma die within 3 years of diagnosis. All patients with high grade glioma experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). We have shown in previous phase I trials that a single Superselective Intra-arterial Cerebral Infusion (SIACI) of Cetuximab and/or Bevacizumab is safe for the treatment of recurrent glioblastoma multiforme (GBM) in adults, and we are currently evaluating the efficacy of this treatment. Therefore, this phase I/II clinical research trial is an extension of that trial in that we seek to test the hypothesis that intra-arterial Cetuximab and Bevacizumab is safe and effective in the treatment of relapsed/refractory glioma in patients <22 years of age. We expect that this project will provide important information regarding the utility of SIACI Cetuximab and Bevacizumab therapy for malignant glioma in patients <22 years of age and may alter the way these drugs are delivered to our patients in the near future.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligoastrocytoma
  • Brain Stem Glioma
  • Fibrillary Astrocytoma
  • Glioblastoma
  • Oligodendroglioma
  • Pilomyxoid Astrocytoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22
  • Official Title: Phase I/II Trial Of Super-Selective Intraarterial Infusion Of Erbitux (Cetuximab) And Avastin (Bevacizumab)For Treatment Of Relapsed/Refractory Intracranial Glioma In Patients Under 22 Years Of Age

Clinical Trial IDs

  • ORG STUDY ID: 1202012214
  • NCT ID: NCT01884740

Conditions

  • Glioblastoma Multiforme
  • Fibrillary Astrocytoma of Brain
  • Glioma of Brainstem
  • Anaplastic Astrocytoma
  • Pilomyxoid Astrocytoma
  • Mixed Oligodendroglioma-Astrocytoma
  • Brain Stem Glioma
  • Diffuse Intrinsic Pontine Glioma

Interventions

DrugSynonymsArms
SIACI of Erbitux and BevacizumabCetuximab, AvastinSIACI of Erbitux and Bevacizumab

Purpose

Central nervous system (CNS) malignancies are the second most common malignancy and the most common solid tumor of childhood, including adolescence. Annually in the United States, approximately 2,200 children are diagnosed with CNS malignancy and rates appear to be increasing. CNS tumors are the leading cause of death from solid tumors in children. Survival duration after diagnosis in children is highly variable depending in part on age at diagnosis, location of tumor, and extent of resection; however, most children with high grade glioma die within 3 years of diagnosis. All patients with high grade glioma experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). We have shown in previous phase I trials that a single Superselective Intra-arterial Cerebral Infusion (SIACI) of Cetuximab and/or Bevacizumab is safe for the treatment of recurrent glioblastoma multiforme (GBM) in adults, and we are currently evaluating the efficacy of this treatment. Therefore, this phase I/II clinical research trial is an extension of that trial in that we seek to test the hypothesis that intra-arterial Cetuximab and Bevacizumab is safe and effective in the treatment of relapsed/refractory glioma in patients <22 years of age. We expect that this project will provide important information regarding the utility of SIACI Cetuximab and Bevacizumab therapy for malignant glioma in patients <22 years of age and may alter the way these drugs are delivered to our patients in the near future.

Detailed Description

      The experimental aspects of this treatment plan will include:

        1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol
           25%; 10 mL over 2 minutes) in order to disrupt the blood brain barrier. This technique
           has been used in several thousand patients in previous studies for the IA delivery of
           chemotherapy for malignant glioma. We have used this without complication in our
           patients from our Phase I protocols as well.

        2. To treat patients <22 years of age with recurring or relapsing glioma with a single
           intraarterial delivery (SIACI) of Cetuximab and Bevacizumab. Our Phase I trials have
           demonstrated the safety of SIACI delivery of these drugs in adults. This trial will
           focus on the safety and efficacy in patients <22 years of age.
    

Trial Arms

NameTypeDescriptionInterventions
SIACI of Erbitux and BevacizumabExperimentalSuperselective Intraarterial Cerebral Infusion (SIACI) of Erbitux (200 m/m2) and Bevacizumab (15 mg/kg)
  • SIACI of Erbitux and Bevacizumab

Eligibility Criteria

        Inclusion:

          1. Male or female patients, under 22 years of age, with a documented histologic
             diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic
             astrocytoma (AA), fibrillary astrocytomas (FA), pilomyxoid astrocytoma (PXA),
             oligodendroglioma, or anaplastic mixed oligoastrocytoma (AOA), or radiologically
             diagnosed brainstem glioma

          2. Patients must have at least one confirmed and evaluable tumor site.

             *A confirmed tumor site is one in which is biopsy-proven with the exception of
             brainstem glioma which will be eligible with radiographic diagnosis. NOTE:
             Radiographic procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing
             lesions must have been performed within three weeks of treatment on this research
             study.

          3. Patients must have a Karnofsky or Lansky performance status 70%. Karnofsky is used
             for patients older than or equal to the age of 16 years and Lansky for those under 16
             years old and an expected survival three months.

          4. No chemotherapy for three weeks prior to treatment under this research protocol and
             no external beam radiation for eight weeks prior to treatment under this research
             protocol.

          5. Patients must have adequate hematologic reserve with absolute neutrophils greater
             than or equal to 1000/mm3 and platelets greater than or equal 100,000/mm3.

          6. Pre-enrollment chemistry parameters must show: bilirubin less than 1.5X the
             institutional upper limit of normal (IUNL); AST or ALT less than 2.5X IUNL and
             creatinine less than 1.5X IUNL.

          7. Pre-enrollment coagulation parameters (PT and PTT) must be less than 1.5X the IUNL.

          8. Concomitant Medications:

             Growth factor(s): Must not have received within 1 week of entry onto this study.

             Steroids: Systemic corticosteroid therapy is permissible in patients with CNS tumors
             for treatment of increased intracranial pressure or symptomatic tumor edema. Patients
             with CNS tumors who are receiving dexamethasone must be on a stable or decreasing
             dose for at least 1 week prior to study entry.

          9. Patients of reproductive age must agree to use a medically effective method of
             contraception during and for a period of three months after the treatment period. A
             pregnancy test will be performed on each premenopausal female of childbearing
             potential immediately prior to entry into the research study.

         10. Patients or their parents/guardians must be able to understand and give written
             informed consent. Informed consent must be obtained at the time of patient screening.

         11. Because of known concerns with Avastin and wound healing, craniotomy patients are
             eligible for the treatment if they have had a craniotomy greater than two weeks prior
             to IA therapy. Craniotomy or major procedure after SIACI Avastin therapy should wait
             4 weeks. Minor surgeries may be performed after two weeks.

        Exclusion:

          1. Previous treatment with Avastin and Cetuximab

          2. Females who are pregnant or lactating.

          3. Females of childbearing potential and fertile men will be informed as to the
             potential risk of procreation while participating in this research trial and will be
             advised that they must use effective contraception during and for a period of three
             months after the treatment period. If they do not agree, they will be ineligible for
             the study.

          4. Patients with significant concurrent medical or psychiatric conditions that would
             place them at increased risk or affect their ability to receive or comply with
             treatment or post-treatment clinical monitoring.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicities
Time Frame:2 Years
Safety Issue:
Description:The descriptive frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to the NCI Common Toxicity Criteria, version 4.0. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.

Secondary Outcome Measures

Measure:Composite Overall Response Rate (CORR)
Time Frame:6 Months
Safety Issue:
Description:The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. We will define "evaluable" patients as patients who met eligibility requirements and have initiated therapy.
Measure:Progression-free survival (PFS)
Time Frame:2 Years
Safety Issue:
Description:PFS will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time. PFS will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of progression.
Measure:Overall Survival (OS)
Time Frame:2 Years
Safety Issue:
Description:Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • GBM
  • AA
  • FA
  • PXA
  • AOA
  • High grade glioma

Last Updated

January 12, 2017