Description:
Primary brain cancer kills up to 10,000 Americans a year. These brain tumors are typically
treated by surgery, radiation therapy and chemotherapy, either individually or in
combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate
for brain cancer patients, with median survival at approximately 12 months. Glioma is the
most common form of primary brain cancer, afflicting approximately 7,000 patients in the
United States each year. These highly malignant cancers remain a significant unmet clinical
need in oncology. GBM often has a high expression EFGR (Epidermal Growth Factor Receptor)
which is blocked by Cetuximab (CTX). The investigators have recently completed a separate
Phase I clinical trial using superselective intra-arterial cerebral infusion (SIACI) of CTX
after blood brain barrier disruption (BBBD) for recurrent GBM (Chakraborty et al, in
revision, Journal of Neurooncology). The investigators found that intra-arterial infusion of
CTX is well tolerated with few adverse effects. The investigators hypothesize that in
patients with newly diagnosed GBM, repeated SIACI of this drug after BBBD will be safe and
efficacious for our patients when combined with standard chemoradiation (STUPP protocol).
This trial will be a non-randomized open label Phase I/II clinical trial. In addition to
standard chemotherapy and radiation therapy (STUPP protocol) the patient will be given CTX
intra-arterially after BBBD for a total of three doses at approximately post surgery days 30,
120 and 210.
Title
- Brief Title: Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma
- Official Title: Phase I/II Trial of Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma
Clinical Trial IDs
- ORG STUDY ID:
HS16-0257
- NCT ID:
NCT02861898
Conditions
- Glioblastoma
- Brain Cancer
- Brain Neoplasm
- Brain Tumor
- Brain Neoplasm, Malignant
- EGFR Gene Overexpression
- GBM
Interventions
| Drug | Synonyms | Arms |
|---|
| Intra-arterial Cetuximab | | Intra-arterial Cetuximab after BBBD |
| Intra-arterial Mannitol | | Intra-arterial Cetuximab after BBBD |
Purpose
Primary brain cancer kills up to 10,000 Americans a year. These brain tumors are typically
treated by surgery, radiation therapy and chemotherapy, either individually or in
combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate
for brain cancer patients, with median survival at approximately 12 months. Glioma is the
most common form of primary brain cancer, afflicting approximately 7,000 patients in the
United States each year. These highly malignant cancers remain a significant unmet clinical
need in oncology. GBM often has a high expression EFGR (Epidermal Growth Factor Receptor)
which is blocked by Cetuximab (CTX). The investigators have recently completed a separate
Phase I clinical trial using superselective intra-arterial cerebral infusion (SIACI) of CTX
after blood brain barrier disruption (BBBD) for recurrent GBM (Chakraborty et al, in
revision, Journal of Neurooncology). The investigators found that intra-arterial infusion of
CTX is well tolerated with few adverse effects. The investigators hypothesize that in
patients with newly diagnosed GBM, repeated SIACI of this drug after BBBD will be safe and
efficacious for our patients when combined with standard chemoradiation (STUPP protocol).
This trial will be a non-randomized open label Phase I/II clinical trial. In addition to
standard chemotherapy and radiation therapy (STUPP protocol) the patient will be given CTX
intra-arterially after BBBD for a total of three doses at approximately post surgery days 30,
120 and 210.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Intra-arterial Cetuximab after BBBD | Experimental | Mannitol 20% 12.5ml over two minutes for Blood Brain Barrier (BBB) disruption followed by CTX administered intra-arterially for three doses at a dose of 250mg/m2 | - Intra-arterial Cetuximab
- Intra-arterial Mannitol
|
Eligibility Criteria
Inclusion Criteria:
- Male or female patients of ≥18 years of age.
- Patients with a documented histologic diagnosis of newly diagnosed glioblastoma
multiforme (GBM)
- Patients with pathology confirmed histologic EGFR overexpression
- Patients must have at least one confirmed and evaluable tumor site.∗
*A confirmed tumor site is one in which is biopsy-proven. NOTE: Radiographic
procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing lesions must have
been performed within two weeks of treatment on this research study.
- Patients must have a Karnofsky performance status ≥70% (or the equivalent ECOG level
of 0-2) and an expected survival of ≥ three months.
- No chemotherapy for two 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 WBC≥3000/mm3, absolute
neutrophils ≥1500/mm3 and platelets ≥100,000/ mm3. Patients who are on Coumadin must
have a platelet count of ≥150,000/ mm3
- Pre-enrollment chemistry parameters must show: bilirubin<1.5X the institutional upper
limit of normal (IUNL); AST or ALT<2.5X IUNL and creatinine<1.5X IUNL.
- Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5X the IUNL.
- Patients 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 must be able to understand and give written informed consent. Informed
consent must be obtained at the time of patient screening.
Exclusion Criteria:
- Women who are pregnant or lactating.
- Women of childbearing potential and fertile men will be informed as to the potential
risk of conception 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.
- Patients with significant intercurrent 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
- Patients with radiological evidence of leptomeningeal disease.
- Patients with history of allergic reaction to CTX
- Patients who initiated or completed chemo/RT
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | The 6-month PFS will be estimated by calculating the proportion of patients who are alive at 6 months from treatment commencement and are progression-free. |
Secondary Outcome Measures
| Measure: | Composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | Subjects will be classified according to the RANO criteria, which is a composite of MRI changes, clinical response and changes in steroid use. |
| Measure: | Toxicities graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03 |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03 |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Northwell Health |
Trial Keywords
- EGFR
- Epidermal Growth Factor Receptor
- EGFRvIII
Last Updated
September 10, 2020
