Description:
Primary 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 of EFGR
(Epidermal Growth Factor Receptor), which is associated with poor prognosis. Several methods
of inhibiting this receptor have been tested, including monoclonal antibodies, vaccines, and
tyrosine kinase inhibitors. The investigators hypothesize that in patients with recurring
GBM, intracranial superselective intra-arterial infusion of Cetuximab (CTX), at a dose of
250mg/m2 in conjunction with hypofractionated radiation, will be safe and efficacious and
prevent tumor progression in patients with recurrent, residual GBM.
Title
- Brief Title: Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA
- Official Title: Phase II Trial of Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory Glioblastoma Multiforme, Anaplastic Astrocytoma, and Anaplastic Oligoastrocytoma
Clinical Trial IDs
- ORG STUDY ID:
HS16-0181
- NCT ID:
NCT02800486
Conditions
- Glioblastoma
- Anaplastic Astrocytoma
- Anaplastic Oligoastrocytoma
- Glioma
- Brain Neoplasm
- Brain Cancer
- Brain Tumor
- Brain Tumor, Recurrent
- Brain Neoplasm, Malignant
Interventions
| Drug | Synonyms | Arms |
|---|
| Intra-arterial Cetuximab | | Intra-arterial Cetuximab with Re-Irradiation |
| Intra-arterial Mannitol | | Intra-arterial Cetuximab with Re-Irradiation |
Purpose
Primary 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 of EFGR
(Epidermal Growth Factor Receptor), which is associated with poor prognosis. Several methods
of inhibiting this receptor have been tested, including monoclonal antibodies, vaccines, and
tyrosine kinase inhibitors. The investigators hypothesize that in patients with recurring
GBM, intracranial superselective intra-arterial infusion of Cetuximab (CTX), at a dose of
250mg/m2 in conjunction with hypofractionated radiation, will be safe and efficacious and
prevent tumor progression in patients with recurrent, residual GBM.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Intra-arterial Cetuximab with Re-Irradiation | Experimental | Mannitol 20% 12.5ml over two minutes for blood brain barrier (BBB) disruption followed by Cetuximab administered intra-arterially for three doses at a dose of 250 mg/m2 combined with hypofractionated re-irradiation | - 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 relapsed or refractory glioblastoma
multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic oligoastrocytoma (AOA)
- 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
- Patients must have a Karnofsky performance status ≥60% 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 of the potential
unknown 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 completed chemo/RT less than 6 months prior to enrollment
- Patients who have not failed standard Stupp protocol
| 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 Evaluation Criteria In Solid Tumors (RECIST) |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | Subjects will be classified according to the RECIST 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 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Northwell Health |
Last Updated
September 10, 2020
