Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22
| Status: | Recruiting |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 1 - 21 |
| Updated: | 2/8/2019 |
| Start Date: | June 2013 |
| End Date: | January 2025 |
| Contact: | Jeffrey Greenfield, MD PhD |
| Email: | jab2029@med.cornell.edu |
| Phone: | 212-746-1996 |
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
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.
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.
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.
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.
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.
We found this trial at
1
site
New York, New York 10021
Phone: 212-746-2363
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