Cetuximab + Reirradiation for Brain Cancer

Overseen By John Boockvar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwell Health

Disqualifiers: Pregnancy, Leptomeningeal disease, Allergic to CTX, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for people with recurring glioblastoma multiforme (GBM), a common and aggressive brain cancer. The trial combines Cetuximab, a drug believed to block cancer growth, with targeted radiation therapy. It aims to determine if this combination can safely and effectively slow tumor progression. Individuals with a confirmed GBM diagnosis who have not responded to standard treatments might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using Cetuximab, a type of antibody treatment, along with re-irradiation for brain cancer is safe and generally well-tolerated. Studies have found that administering Cetuximab directly into the brain's blood vessels does not cause serious side effects. Patients usually tolerate doses up to 250 mg/m² without major problems. This approach has been tested in people with recurring brain tumors, and the results have been promising. Although still under study, the safety information collected so far suggests this combination could offer hope for those with difficult-to-treat brain cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about the treatment combining Cetuximab with reirradiation for brain cancer because it introduces a unique delivery method and targets the tumor more directly. Unlike standard treatments that typically involve systemic chemotherapy, this approach administers Cetuximab intra-arterially, allowing a higher concentration of the drug to reach the tumor by temporarily disrupting the blood-brain barrier. This targeted delivery could potentially enhance effectiveness and reduce side effects. Additionally, the use of hypofractionated re-irradiation aims to deliver radiation more precisely, minimizing damage to healthy tissue while attacking the cancer cells.

What evidence suggests that Cetuximab with reirradiation might be an effective treatment for brain cancer?

Research suggests that Cetuximab, when combined with repeated radiation therapy, may help treat brain cancer such as glioblastoma (GBM). GBM often exhibits high levels of a protein called EGFR, which can make the cancer more aggressive. Cetuximab is designed to block EGFR, potentially slowing tumor growth. In this trial, participants will receive intra-arterial Cetuximab with hypofractionated re-irradiation. Early studies with Cetuximab have shown promise in treating cancers with high EGFR levels. Combining this with targeted repeated radiation might improve outcomes for patients with recurring GBM. Although more research is needed, this combination aims to address the urgent need for better brain cancer treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

John Boockvar, MD

Principal Investigator

Northwell Health

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

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 history of allergic reaction to CTX

I do not have any major health or mental conditions that would make treatment risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-arterial Cetuximab with hypofractionated re-irradiation for three doses

6 months

Multiple visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up visits

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Hypofractionated re-irradiation

Trial Overview 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.

How Is the Trial Designed?

Group I: Intra-arterial Cetuximab with Re-Irradiation Experimental Treatment 3 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

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Published Research Related to This Trial

The study demonstrated that radiolabeled cetuximab (131I-Erbi) is stable for up to 72 hours and shows significantly higher uptake in cancer cells with epidermal growth factor receptors, indicating its potential effectiveness in targeting brain metastases.

Combining radiotherapy with 131I-Erbi resulted in a greater inhibition of tumor cell proliferation compared to using cetuximab alone, suggesting a synergistic effect that could enhance treatment outcomes for patients with multiple brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioactive EGFR antibody cetuximab in multimodal cancer treatment: stability and synergistic effects with radiotherapy. Rades, D., Wolff, C., Nadrowitz, R., et al.[2018]

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

Cetuximab, a monoclonal antibody targeting EGFR, effectively delivered boron to brain tumors, achieving significantly higher boron concentrations in gliomas compared to traditional delivery methods, with mean concentrations of 92.3 microg/g in F98(EGFR) gliomas.

Rats treated with boronated cetuximab showed a mean survival time of 45 days, which increased to over 59 days when combined with another boron delivery agent, indicating its potential as an effective treatment for gliomas in neutron capture therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent. Barth, RF., Wu, G., Yang, W., et al.[2018]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

Cetuximab, a treatment for advanced colorectal cancer, can lead to severe corneal erosion, as seen in a 62-year-old patient, despite ongoing conservative treatment.

Topical application of human EGF eye drops effectively promoted corneal healing, closing epithelial defects within 7 to 19 days, allowing continued cetuximab treatment and potentially preventing further complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Topical application of EGF for the therapy of persisting corneal erosion under cetuximab treatment]. Förster, CG., Cursiefen, C., Kruse, FE.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02800486?term=AREA%5BConditionSearch%5D(Anaplastic%20oligoastrocytoma%20OR%20%22aMOA%22%20OR%20%22%20anaplastic%20mixed%20glioma%22%20OR%20%22%20WHO%20grade%20III%20mixed%20glioma%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=2

Super Selective Intra-arterial Repeated Infusion of ... Study Overview. Brief Summary. Primary brain tumors are typically treated by surgery, radiation therapy and chemotherapy, either individually or in combination.

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/115764

Super Selective Intra-arterial Repeated Infusion of ... Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months.

3. withpower.com withpower.com/trial/phase-3-astrocytoma-4-2016-65944

Cetuximab + Reirradiation for Brain Cancer This Phase 2 medical study run by Northwell Health is evaluating whether Cetuximab and Hypofractionated re-irradiation will have tolerable side effects ...

4. meghan-johnson-scholarship-fund.clinicaltrialconnect.com meghan-johnson-scholarship-fund.clinicaltrialconnect.com/trials/NCT02800486

Super Selective Intra-arterial Repeated Infusion of Cetuximab ... Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10449695/

Prospective randomized clinical studies involving reirradiation We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26945581/

Superselective intraarterial cerebral infusion of cetuximab ... SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated.

7. trials.braintumor.org trials.braintumor.org/trials/NCT02861898

Super-selective Intra-arterial Repeated Infusion of Cetuximab ... Repeated SIACI of this drug after BBBD will be safe and efficacious for our patients when combined with standard chemoradiation (STUPP protocol).

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.950167/pdf

A systematic review on intra- arterial cerebral infusions of ... A Phase I study has demonstrated promising results, which should be further evaluated by ongoing 3 phase II clinical trials for glioma ( ...