Cetuximab After Immunotherapy for Head and Neck Cancer

Overseen By Study Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: PD-1 inhibitors

Must not be taking: Investigational agents

Disqualifiers: Interstitial lung disease, Cardiac disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II treatment, non-randomized, open label clinical trial to study the efficacy of the Cetuximab when administered as single agent in recurrent/ metastatic head and neck squamous cell carcinoma after the failure or intolerance of immuno-oncology or immuno-oncology combined with chemotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are on medications that might interact with Cetuximab and need to be continued.

What data supports the effectiveness of the drug Cetuximab for head and neck cancer?

Cetuximab has been shown to be effective in treating head and neck squamous cell carcinoma (HNSCC) as it targets the epidermal growth factor receptor (EGFR), which is important in cancer growth. It was FDA-approved for use in HNSCC in 2006, and studies have confirmed its efficacy, especially in patients who are not suitable for other chemotherapy options. ^{1 2 3 4 5}

Is cetuximab safe for humans?

Cetuximab has been used in humans for treating cancers like colorectal and head and neck cancer. Some patients experience skin rashes and dermatitis (skin irritation) as side effects, but it has been generally considered safe for use in these conditions. ^{2 6 7 8 9}

How is the drug Cetuximab unique for treating head and neck cancer?

Cetuximab is unique because it is a monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), which plays a crucial role in the growth of many cancers, including head and neck cancer. It was approved for use in combination with chemoradiation therapy for locally advanced head and neck cancer, offering an alternative to traditional chemotherapy for patients who may not tolerate it well. ^{1 2 3 4 10}

Research Team

Mercedes Porosnicu

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults with head and neck squamous cell carcinoma that has come back or spread after immunotherapy, possibly combined with chemo. They should be in a condition to perform daily activities (Performance Status 0-2), able to give blood and saliva samples, and agree to follow the study rules. Pregnant individuals, those who've had certain heart issues or lung diseases recently, or have had allergic reactions to similar drugs are not eligible.

Inclusion Criteria

Must have measurable disease by scans- at least one measurable lesion

My cancer is confirmed as squamous cell carcinoma in the head or neck.

I have been treated with immunotherapy targeting PD-1, alone or with chemotherapy.

Exclusion Criteria

I do not have any serious wounds, ulcers, or bone fractures that are not healing.

I haven't had serious heart issues or procedures in the last 6 months.

Prior allergic reaction to Cetuximab

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive cetuximab intravenously over 60-120 minutes once every week in the absence of disease progression or unacceptable toxicity

Up to 2 years

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week and then every 6-8 weeks thereafter

1 visit (in-person) at 1 week, then every 6-8 weeks

Treatment Details

Interventions

• Cetuximab

Trial Overview The trial tests Cetuximab's effectiveness as a single agent in patients whose cancer didn't respond well to prior treatments involving PD-1 inhibitors. It's an open-label Phase II study where everyone knows they're getting Cetuximab; there’s no placebo group. Participants will also undergo quality of life assessments through questionnaires.

Participant Groups

Group I: Cetuximab Experimental Treatment 3 Interventions

Patients receive cetuximab IV over 60-120 minutes once every week in the absence of disease progression or unacceptable toxicity.

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 32 head and neck squamous cell carcinoma (HNSCC) cell lines, researchers identified YAP1 amplification as a key factor associated with resistance to the EGFR-targeting antibody cetuximab, suggesting it could serve as a novel biomarker for treatment response.

The study demonstrated that higher levels of YAP1 not only correlated with cetuximab resistance but also that reducing YAP1 expression through RNA knockdown increased sensitivity to the drug, highlighting its potential role in guiding therapy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. Jerhammar, F., Johansson, AC., Ceder, R., et al.[2021]

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]

The ERBITAX regimen (paclitaxel and cetuximab) demonstrated a response rate of 37.7% in 531 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who were ineligible for cisplatin-based chemotherapy, indicating its efficacy as a first-line treatment.

Patients who received immunotherapy after ERBITAX treatment had significantly improved overall survival (OS) of 29.8 months compared to 13.8 months for those receiving other treatments, suggesting a beneficial sequential treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck. Rubió-Casadevall, J., Cirauqui Cirauqui, B., Martinez Trufero, J., et al.[2023]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, has shown repeated effectiveness in treating a patient with nonresectable squamous cell skin cancer, which is significant given the poor prognosis of advanced cases.

This case suggests that cetuximab could be a valuable treatment option for patients with squamous cell carcinomas that express the epidermal growth factor receptor, particularly in palliative care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Suen, JK., Bressler, L., Shord, SS., 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]

In a study of 602 patients with head and neck squamous cell carcinoma, those who developed a grade 2 to 4 skin rash from cetuximab treatment had significantly better overall survival and reduced rates of distant metastasis, particularly in patients with p16-negative tumors.

However, patients experiencing more severe acute radiation dermatitis (grade 2 to 4) were more likely to develop late skin fibrosis, indicating a potential trade-off between immediate treatment effects and long-term skin toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience. Bar-Ad, V., Zhang, QE., Harari, PM., et al.[2019]

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]

The use of chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) significantly increased from 29% in 2001 to 61% in 2009, indicating a growing acceptance of this treatment approach.

Since the approval of cetuximab in 2006, it has become the most commonly used agent in CRT, suggesting that it may have contributed to the increased use of CRT, particularly among older and sicker patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in chemoradiation use in elderly patients with head and neck cancer: Changing treatment patterns with cetuximab. Baxi, SS., O'Neill, C., Sherman, EJ., et al.[2022]

References

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

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. [2021]

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

Cetuximab. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. [2022]

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

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience. [2019]

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

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]

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

Trends in chemoradiation use in elderly patients with head and neck cancer: Changing treatment patterns with cetuximab. [2022]