AzTrials
AzTrials

Glioblastoma MultiformePhase 1/2NCT01884740

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

A Phase 1/2 study testing SIACI of Erbitux and Bevacizumab in people with Glioblastoma Multiforme and Fibrillary Astrocytoma of Brain, run by Weill Medical College of Cornell University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
SIACI of Erbitux and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Jun 2013to Oct 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
  • 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.
  • 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.
  • 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.
  • 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.
Show all 14Show fewer
  • 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.
  • Pre-enrollment coagulation parameters (PT and PTT) must be less than 1.5X the IUNL.
  • 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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • Previous treatment with Avastin and Cetuximab
  • Females who are pregnant or lactating.
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medical College/New York Presbyterian Hospital

    New York, New York, 10001

Other trials in United States

About this study

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

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.

Read the 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.
Being tested
SIACI of Erbitux and Bevacizumab
Keywords
GBM, AA, FA, PXA, AOA, High grade glioma
Medical subject headings
Glioblastoma, Astrocytoma, Oligodendroglioma, Diffuse Intrinsic Pontine Glioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SIACI of Erbitux and BevacizumabDrug

    Also called Cetuximab, Avastin

    Subjects will receive a single intra-arterial dose of Cetuximab (200 mg/m^2) and Bevacizumab (15 mg/kg) via Superselective Intraarterial Cerebral Infusion (SIACI).

Study groups in NCT01884740
Study groupRoleWhat they receive
SIACI of Erbitux and BevacizumabExperimentalSuperselective Intraarterial Cerebral Infusion (SIACI) of Erbitux (200 mg/m^2) and Bevacizumab (15 mg/kg)
Receives: Drug: SIACI of Erbitux and Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Overall Survival (OS)

    Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.

    Measured: 2 Years

  2. Composite Overall Response Rate (CORR)

    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.

    Measured: 6 Months

Secondary outcomes (2)

  1. Number of Treatment Emergent Adverse Events

    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.

    Measured: 28 days

  2. Median Progression-free Survival (PFS)

    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.

    Measured: 2 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionOct 2018
  4. Study completionOct 2018

Why it stopped: The study was prematurely closed in December 2021 due to low accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01884740
Sponsor's protocol ID
1202012214
Status last verified
Jul 2022
First submitted
19 Jun 2013
Last updated
9 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • McCrea HJ, Ivanidze J, O'Connor A, Hersh EH, Boockvar JA, Gobin YP, Knopman J, Greenfield JP. Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial. J Neurosurg Pediatr. 2021 Aug 6;28(4):371-379. doi: 10.3171/2021.3.PEDS20738. Print 2021 Oct 1.

    PubMed 34359048

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SIACI of Erbitux and Bevacizumab in people with Glioblastoma Multiforme and Fibrillary Astrocytoma of Brain, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Overall Survival (OS) (time frame: 2 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01884740, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in