Phase I/II Trial Of Super-Selective Intraarterial Infusion Of Erbitux and Bevacizumab For Treatment Of Relapsed/Refractory Intracranial Glioma In Patients Under 22 Years Of Age

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Weill Medical College of Cornell University
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01884740
First received: June 19, 2013
Last updated: July 31, 2013
Last verified: July 2013
  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.


Condition Intervention Phase
Glioblastoma Multiforme
Fibrillary Astrocytoma of Brain
Glioma of Brainstem
Anaplastic Astrocytoma
Pilomyxoid Astrocytoma
Mixed Oligodendroglioma-Astrocytoma
Brain Stem Glioma
Diffuse Intrinsic Pontine Glioma
High Grade Glioma
Drug: SIACI of Erbitux (200 m/m2) and Bevacizumab(15 mg/kg)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Toxicities [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.


Estimated Enrollment: 30
Study Start Date: June 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SIACI of Erbitux and Bevacizumab
Superselective Intraarterial Cerebral Infusion (SIACI) of Erbitux (200 m/m2) and Bevacizumab(15 mg/kg)
Drug: SIACI of Erbitux (200 m/m2) and Bevacizumab(15 mg/kg)
Other Names:
  • Cetuximab
  • Avastin

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.
  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria for 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.

Criteria for 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01884740

Contacts
Contact: Jeffrey Greenfield, MD PhD 212-746-1996 jab2029@med.cornell.edu
Contact: Melissa Ricketts 212-746-7373 mdr2001@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College/New York Presbyterian Hospital Recruiting
New York, New York, United States, 10001
Contact: Jeffrey Greenfield, MD PhD    212-746-2363    jpgreenf@med.cornell.edu   
Contact: Melissa Ricketts    212-746-7373    mdr2001@med.cornell.edu   
Sub-Investigator: Mark Souweidane, MD         
Sub-Investigator: Y. Pierre Gobin, MD         
Sub-Investigator: Athos Patsalides, MD         
Sub-Investigator: Paul Christos, Dr.P.H., M.S         
Sub-Investigator: Heather McCrea, MD PhD         
Sub-Investigator: Kaleb Yohay, MD         
Sub-Investigator: Maria Rust, PNP         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Jeffery Greenfield, MD PhD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01884740     History of Changes
Other Study ID Numbers: 1202012214
Study First Received: June 19, 2013
Last Updated: July 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
GBM
AA
FA
PXA
AOA

Additional relevant MeSH terms:
Glioma
Astrocytoma
Glioblastoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Cetuximab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014