Cetuximab + Interleukin-12 for Head and Neck Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Investigational agents

Disqualifiers: Brain metastases, Uncontrolled illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, cetuximab and recombinant interleukin-12, to evaluate their effectiveness against head and neck cancer that has recurred, metastasized, or cannot be surgically removed. Cetuximab, a monoclonal antibody, aids the immune system in fighting cancer, while interleukin-12 boosts white blood cells to target tumor cells. The trial aims to determine the optimal dose and understand any side effects of this combination. Individuals with squamous cell carcinoma of the head and neck, whose cancer has returned or spread and cannot be removed, may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the trial.

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

Research has shown that combining cetuximab and recombinant interleukin-12 has been tested for safety in treating head and neck cancer. Early results suggest that patients tolerate this combination well. Cetuximab helps the immune system fight cancer, while recombinant interleukin-12 strengthens the body's immune response.

Studies observed some side effects, but they were generally manageable. Common side effects included skin reactions and tiredness, typical with cetuximab. Recombinant interleukin-12 might cause flu-like symptoms, but these were usually mild. Overall, researchers considered the combination safe enough to continue in clinical trials.

This suggests a promising safety profile, but potential trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cetuximab and Recombinant Interleukin-12 for head and neck cancer because it offers a unique approach compared to existing treatments. Unlike standard therapies that primarily focus on targeting cancer cells directly, Cetuximab is an antibody that blocks a protein called EGFR, which can slow down tumor growth. Recombinant Interleukin-12 adds an innovative twist by boosting the immune system's ability to fight cancer, potentially leading to more effective and longer-lasting results. This dual action—targeting cancer cells while ramping up the body's own defenses—sets this treatment apart and has researchers hopeful for improved patient outcomes.

What evidence suggests that cetuximab and recombinant interleukin-12 could be effective for head and neck cancer?

This trial will study the combination of cetuximab and recombinant interleukin-12 for treating head and neck cancer. Research shows that cetuximab may help the immune system attack cancer cells by targeting a protein called EGFR on their surface. Interleukin-12 may help white blood cells destroy tumor cells. Early results suggest that this combination boosts the body's defense against cancer. However, past studies have not demonstrated clear benefits with this combination. More research is needed to fully understand its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

William E Carson

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with squamous cell carcinoma of the head and neck that's recurrent, metastatic, or inoperable. They must understand the study and consent to it, have a certain level of physical fitness (ECOG <=2), normal kidney function or specific creatinine clearance, no recent chemotherapy or radiotherapy, not be on other investigational drugs, and have no uncontrolled illnesses. Women who are pregnant or breastfeeding are excluded.

Inclusion Criteria

My cancer in the head or neck area has returned or spread and cannot be removed by surgery.

You are expected to live for more than 6 months.

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks, or I've recovered from its side effects.

My brain cancer has been stable for 3 months without needing steroids.

You have had allergic reactions to drugs similar to IL-12 or other drugs used in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cetuximab intravenously on day 1 and recombinant interleukin-12 subcutaneously on days 2 and 5, repeating every 2 weeks for 12 courses

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Recombinant Interleukin-12

Trial Overview The trial is testing how well recombinant interleukin-12 works with cetuximab in treating this type of cancer. It looks at side effects and best doses. Interleukin-12 may boost white blood cells to fight cancer while cetuximab could help the immune system attack cancer cells more effectively.

How Is the Trial Designed?

Group I: Treatment (cetuximab and recombinant interleukin-12) Experimental Treatment 3 Interventions

Patients receive cetuximab IV over 1-2 hours on day 1 and recombinant interleukin-12 SC on days 2 and 5 beginning in course 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical response or stable disease may continue with therapy until disease progression.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cetuximab is an effective monoclonal antibody that targets the epidermal growth factor receptor, which is linked to poor outcomes in solid tumors, by blocking its activation and associated oncogenic processes.

While cetuximab can cause infusion reactions and skin-related side effects, its overall safety profile is favorable compared to traditional chemotherapy, and these side effects are generally manageable with appropriate treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: adverse event profile and recommendations for toxicity management. Thomas, M.[2020]

Cétuximab, a monoclonal antibody targeting EGFR, has been shown to improve overall survival in patients with locally advanced head and neck cancer when used alongside radiotherapy, and is now reimbursed in Belgium under specific conditions.

In metastatic head and neck cancer, adding cétuximab to platinum-based chemotherapy has demonstrated improved overall survival compared to chemotherapy alone, marking a significant advancement in treatment options, although it is not yet available to Belgian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monoclonal antibodies for the treatment of head and neck cancer]. Sautois, B., Martin, M., Demez, P., 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 shown to improve survival rates when used alongside radiation therapy for patients with locally-advanced head and neck cancer, as demonstrated in a landmark study.

In recurrent and metastatic cases, cetuximab also enhances the effectiveness of chemotherapy, indicating its significant role in the treatment of squamous cell carcinoma of the head and neck, although further research is needed to optimize its use and identify the best patient candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the management of head and neck cancers. Kabolizadeh, P., Kubicek, GJ., Heron, DE., et al.[2020]

In a study analyzing 3,086 reports of adverse events from cetuximab therapy for head and neck cancer, 89% of the events were classified as serious, with mucosal inflammation being the most common issue.

The study identified that receiving cetuximab treatment outside the US and using it alongside other medications significantly increased the risk of serious adverse outcomes, highlighting the need for careful monitoring in these situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes. Stanbouly, D., Philipone, E., Morlandt, AB., et al.[2022]

In a study of 99 head-and-neck cancer patients receiving simultaneous integrated boost intensity-modulated radiotherapy with cetuximab, 34% experienced severe dermatitis (Grade 3/4), significantly higher than the 3% in a control group treated with cisplatin.

There was a clear link between the radiation dose to the skin and the severity of dermatitis in patients receiving cetuximab, indicating that higher radiation exposure increases the risk of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Studer, G., Brown, M., Salgueiro, EB., et al.[2015]

Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), shows only modest effectiveness as a standalone treatment for advanced non-small cell lung cancer (NSCLC), with limited benefits when added to chemotherapy based on phase II studies.

However, cetuximab has demonstrated improved survival rates when combined with radiotherapy in head and neck cancer, and ongoing research is exploring its potential benefits in combination with other treatments for locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for cetuximab in non small cell lung cancer? Morgensztern, D., Govindan, R.[2018]

In a study involving 201 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the two-drug regimen of cetuximab plus cisplatin (CetCis) demonstrated noninferior progression-free survival (PFS) compared to the three-drug regimen that included paclitaxel (CetCisPac), with median PFS of 6 months versus 7 months, respectively.

The CetCis regimen also showed a lower rate of grade 4 toxicities (14% compared to 33% in the CetCisPac group), indicating a potentially safer treatment option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Bossi, P., Miceli, R., Locati, LD., et al.[2023]

Cetuximab, an anti-HER1 monoclonal antibody, effectively enhances the immune response against squamous cell carcinoma of the head and neck by activating natural killer (NK) cells, leading to significant tumor cell lysis.

The addition of interleukin-12 (IL-12) to cetuximab treatment markedly improves NK cell activity and cytokine production, resulting in reduced tumor burden in a murine model, suggesting that IL-12 could be a beneficial adjuvant in treating HER1-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab therapy in head and neck cancer: immune modulation with interleukin-12 and other natural killer cell-activating cytokines. Luedke, E., Jaime-Ramirez, AC., Bhave, N., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6697573/

A phase I/II trial of cetuximab in combination with ... Experimental Design: This phase I/II trial evaluated the combination of cetuximab with IL-12 for the treatment of EGFR-expressing head and neck cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01468896

Cetuximab and Recombinant Interleukin-12 in Treating ... This phase I/II trial studies the side effects and best dose of recombinant interleukin-12 when given together with cetuximab and to see how well they work ...

3. withpower.com withpower.com/trial/phase-2-squamous-cell-carcinoma-of-head-and-neck-9-2011-053f5

Cetuximab + Interleukin-12 for Head and Neck Cancer This phase I/II trial studies the side effects and best dose of recombinant interleukin-12 when given together with cetuximab and to see how well they work ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1053429625000098

Metastatic Head and Neck Cancer: Immunotherapy and ... Prior trials evaluating the combination of cetuximab plus a recombinant IL-12 failed to demonstrate any clinical responses. ... head and neck squamous cell ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3432674/

Cetuximab Therapy in Head and Neck Cancer We hypothesized that IL-12 would enhance the anti-tumor activity of the anti-HER1 antibody cetuximab against squamous cell carcinomas of the head and neck ...