Cetuximab + Interleukin-12 for Head and Neck Cancer

Recruiting at 1 trial location

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

23 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Cetuximab combined with Interleukin-12 for head and neck cancer?

Cetuximab is effective in treating head and neck cancer by targeting cancer cells that overexpress a specific protein (EGFR) and activating immune cells to attack these cells. Combining Cetuximab with Interleukin-12 may enhance this immune response, potentially improving its effectiveness against cancer. ^{1 2 3 4 5}

What is the safety profile of Cetuximab and Interleukin-12 for head and neck cancer?

Cetuximab is generally considered safe, but it can cause infusion reactions, skin rashes, and nail disorders. Infusion reactions can be serious, so preventive measures are taken, and skin rashes are common but usually manageable. The safety profile of Cetuximab is favorable compared to traditional chemotherapy. ^{1 5 6 7 8}

What makes the drug Cetuximab + Interleukin-12 unique for head and neck cancer?

This drug combination is unique because Cetuximab targets and binds to cancer cells that overexpress the epidermal growth factor receptor (EGFR), while Interleukin-12 boosts the immune system by activating natural killer cells to enhance the anti-tumor effects of Cetuximab. ^{1 2 5 9 10}

What is the purpose of this trial?

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 in treating patients with squamous cell carcinoma of the head and neck that has come back, spread to another place in the body, or cannot be removed by surgery. Recombinant interleukin-12 may stimulate the white blood cells to kill tumor cells. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread Giving recombinant interleukin-12 together with cetuximab may kill more tumor cells.

Research Team

William E Carson

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

2. England pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the management of head and neck cancers. [2020]

3. England 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. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on cetuximab in squamous cell carcinoma of the head and neck. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Cetuximab therapy in head and neck cancer: immune modulation with interleukin-12 and other natural killer cell-activating cytokines. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Is there a role for cetuximab in non small cell lung cancer? [2018]

10. Belgium pubmed.ncbi.nlm.nih.gov

[Monoclonal antibodies for the treatment of head and neck cancer]. [2018]