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

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ClinicalTrials.gov Identifier: NCT01884740
Recruitment Status : Recruiting
First Posted : June 24, 2013
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE June 19, 2013
First Posted Date  ICMJE June 24, 2013
Last Update Posted Date March 10, 2020
Study Start Date  ICMJE June 2013
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2020)
Composite Overall Response Rate (CORR) [ Time Frame: 6 Months ]
The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. The investigator will define "evaluable" patients as patients who met eligibility requirements and have initiated therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2013)
  • Toxicities [ Time Frame: 2 Years ]
    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.
  • Composite Overall Response Rate (CORR) [ Time Frame: 6 Months ]
    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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2020)
  • Number of treatment emergent adverse events [ Time Frame: 2 Years ]
    All treatment emergent adverse events will be assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE)v. 4.0 terminology for severity, duration, and relationship to research protocol treatment.
  • Median Progression-free survival (PFS) [ Time Frame: 2 Years ]
    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.
  • Median Overall Survival (OS) [ Time Frame: 2 Years ]
    Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2013)
  • Progression-free survival (PFS) [ Time Frame: 2 Years ]
    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.
  • Overall Survival (OS) [ Time Frame: 2 Years ]
    Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Fibrillary Astrocytoma of Brain
  • Glioma of Brainstem
  • Anaplastic Astrocytoma
  • Pilomyxoid Astrocytoma
  • Mixed Oligodendroglioma-Astrocytoma
  • Brain Stem Glioma
  • Diffuse Intrinsic Pontine Glioma
Intervention  ICMJE Drug: SIACI of Erbitux and Bevacizumab
Subjects will receive a single intra-arterial dose of Cetuximab (200 m/m2) and Bevacizumab (15 mg/kg) via Superselective Intraarterial Cerebral Infusion (SIACI).
Other Names:
  • Cetuximab
  • Avastin
Study Arms  ICMJE Experimental: SIACI of Erbitux and Bevacizumab
Superselective Intraarterial Cerebral Infusion (SIACI) of Erbitux (200 m/m2) and Bevacizumab (15 mg/kg)
Intervention: Drug: SIACI of Erbitux and Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2013)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2025
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeffrey Greenfield, MD PhD 212-746-1996 jab2029@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01884740
Other Study ID Numbers  ICMJE 1202012214
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffery Greenfield, MD PhD Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP