Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Northwell Health
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
What makes the treatment Cetuximab + Reirradiation unique for brain cancer?
Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which is involved in the growth of many cancers. This treatment is unique because it combines cetuximab with reirradiation, potentially enhancing the effects of radiotherapy by targeting EGFR, which may improve outcomes for brain cancer patients if cetuximab can effectively cross the blood-brain barrier.
12578What data supports the effectiveness of the drug Cetuximab in treating brain cancer?
Research suggests that Cetuximab, when combined with radiotherapy, may have synergistic effects, meaning they work better together, in treating cancers. Although this study was not specifically on brain cancer, it indicates potential benefits if Cetuximab can reach the brain effectively.
24578Do I need to stop my current medications for the trial?
The trial requires that you stop chemotherapy at least two weeks before starting the treatment and avoid external beam radiation for eight weeks prior. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.
Is cetuximab generally safe for use in humans?
Cetuximab has been used in treating metastatic colorectal cancer and is generally considered safe, though it can cause side effects like skin rash, diarrhea, nausea, vomiting, and fatigue. Severe side effects are rare, but skin toxicity and other mild to moderate side effects have been observed.
23567Eligibility Criteria
This trial is for adults over 18 with recurrent brain cancers like GBM, AA, or AOA that have high EGFR levels. They must be in good enough health to participate, not have had recent chemo or radiation therapy, and agree to use contraception. Pregnant women and those with severe medical conditions or allergies to Cetuximab are excluded.Inclusion Criteria
I have a confirmed diagnosis of a specific type of brain tumor that has returned or is not responding to treatment.
I can care for myself and am expected to live for at least three more months.
I haven't had chemotherapy in the last 2 weeks or radiation in the last 8 weeks.
My cancer shows high levels of EGFR.
I have at least one tumor that can be measured and has been confirmed by a biopsy.
My blood counts meet the required levels for treatment.
Exclusion Criteria
I have not failed the standard Stupp protocol for my condition.
I am not pregnant or breastfeeding.
Participant Groups
The study tests if a combination of intra-arterial Cetuximab (a monoclonal antibody) at a specific dose along with hypofractionated re-irradiation can safely treat recurring brain tumors by preventing tumor growth more effectively than current treatments.
1Treatment groups
Experimental Treatment
Group I: Intra-arterial Cetuximab with Re-IrradiationExperimental Treatment3 Interventions
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
Cetuximab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Erbitux for:
- Locally or regionally advanced squamous cell carcinoma of the head and neck
- Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
- BRAF V600E mutation-positive metastatic colorectal cancer
🇪🇺 Approved in European Union as Erbitux for:
- Squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Lenox Hill Brain Tumor CenterNew York, NY
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Who is running the clinical trial?
Northwell HealthLead Sponsor
References
Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent. [2018]Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B(1100)), the mean boron concentration in rats bearing either F98(EGFR) or F98(WT) gliomas were 92.3+/-23.3 microg/g and 36.5+/-18.8 microg/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B(1000)) was 6.7+/-3.6 microg/g. Based on its favorable in vivo uptake, C225-G5-B(1100) was evaluated as a delivery agent for BNCT in F98(EGFR) glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B(1100), administered by convection enhanced delivery (CED), was 45+/-3d compared to 25+/-3d for untreated control animals. A further enhancement in MST to >59d was obtained by administering C225-G5-B(1100) in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.
Cetuximab. [2020]Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb) is a monoclonal antibody that binds to the epidermal growth factor receptor, which is important in the growth of many cancers. In February 2004, it was granted accelerated approval by the US FDA for the treatment of metastatic colorectal cancer on the basis of tumour response rates in Phase II trials.
Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. [2018]Cetuximab (Erbitux) in combination with irinotecan is the most promising combination in heavily pretreated patients with advanced colorectal cancer. Efficacy of this combination was confirmed in the pivotal BOND I study. The aim of the present study was to evaluate efficacy and toxicity of a combination regimen of cetuximab and irinotecan but in contrast to the BOND I study all patients had previously received 5-FU, oxaliplatin and irinotecan and all had progressed during or shortly after completion of treatment. Before January 2005 salvage therapy with cetuximab and irinotecan was not used in Denmark. The Danish government had initiated a national programme for patients with advanced cancer and according to this programme the National Board of Health may approve and finance experimental treatment. From January 2005 to September 2005, 65 consecutive patients were treated with cetuximab (weekly) and irinotecan (each 2 or 3 weeks) at three university hospitals. Median age was 57 years (23-78), and median performance status was 1 (0-3). Response rate was 20%, median TTP was 5.5 months and median OS was 10.4 months. Response and survival was significantly correlated with severity of skin toxicity. Toxicity grade 3 was rare (skin toxicity 8%, diarrhoea 10%, nausea 3%, vomiting 3%, fatigue 8%). Salvage therapy with cetuximab and irinotecan is effective in patients pretreated with irinotecan, and oxaliplatin and in a general population the results from the BOND I study was confirmed.
[Topical application of EGF for the therapy of persisting corneal erosion under cetuximab treatment]. [2021]Cetuximab (Erbitux), a monoclonal epidermal growth factor receptor (EGFR) antibody, has been used for the treatment of advanced colorectal carcinoma over the last two years. Inhibition of EGFR also influences corneal wound healing as EGF stimulates the proliferation of epithelial cells.
Radioactive EGFR antibody cetuximab in multimodal cancer treatment: stability and synergistic effects with radiotherapy. [2018]Systemic therapies when added to whole brain radiotherapy have failed to improve the survival of patients with multiple brain metastases. The epidermal growth factor receptor antibody cetuximab is an attractive option, if it is able to cross the blood-brain barrier. This might be proven with molecular imaging if the radiolabeled antibody is stable long enough to be effective. This study investigated the stability of radiolabeled cetuximab (Erbitux) ((131)I-Erbi) and potential synergistic effects with radiotherapy in vitro.
[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval.
Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]Cetuximab (Erbitux(®)) is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR). In the USA, the approval of cetuximab has been recently expanded to include the first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer (mCRC) when used in combination with FOLFIRI (irinotecan, fluorouracil, leucovorin [folinic acid]). The addition of cetuximab to first-line treatment with FOLFIRI improved progression-free survival, overall survival, and objective response rates relative to treatment with FOLFIRI alone in patients with EGFR-expressing mCRC with KRAS wild-type tumors. Therefore, cetuximab plus FOLFIRI is a useful biomarker-directed option in the first-line treatment of this patient population.