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

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of Cetuximab for individuals with head and neck cancer that has recurred or spread after not responding to previous treatments. The goal is to evaluate how well Cetuximab works when administered alone, particularly after other treatments like immunotherapy or a combination of immunotherapy and chemotherapy have failed. This trial may suit those diagnosed with head and neck squamous cell carcinoma, who have previously tried immunotherapy, and have measurable cancer that can be tracked with scans. As a Phase 2 trial, it focuses on assessing Cetuximab's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective treatment.

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.

Is there any evidence suggesting that Cetuximab is likely to be safe for humans?

Research shows that cetuximab is generally well-tolerated by patients with head and neck cancer. Studies have found that cetuximab can be effective when other treatments have failed. Most patients experience some skin reactions, such as rashes or itching, but these are common and usually manageable.

Cetuximab, when used alongside other treatments, has helped some patients live longer. This makes cetuximab a reliable option for those who haven't responded to other therapies. While side effects can occur, cetuximab's safety is well-documented from its use in other approved treatments.

Overall, cetuximab is considered a relatively safe choice for patients with recurring or spreading head and neck cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard treatments for head and neck cancer, which often include surgery, radiation, and platinum-based chemotherapy, cetuximab offers a different approach by targeting the epidermal growth factor receptor (EGFR). This specific targeting can help block the growth and spread of cancer cells more precisely. Researchers are excited about cetuximab because it provides an option for patients who may not respond well to traditional therapies, especially after immunotherapy. By offering a weekly IV treatment, cetuximab could potentially improve outcomes with a different mechanism of action that directly interferes with cancer cell signaling.

What evidence suggests that Cetuximab might be an effective treatment for head and neck cancer?

Research has shown that Cetuximab effectively treats head and neck cancer. Studies have found that Cetuximab can extend survival when combined with other treatments like radiation or chemotherapy. Even if cancer returns or spreads after treatments such as platinum-based chemotherapy, Cetuximab remains effective. For patients whose cancer hasn't spread extensively, adding Cetuximab to radiation therapy can significantly extend survival. Additionally, those with recurrent cancer often experience better outcomes with Cetuximab treatment. Participants in this trial will receive Cetuximab to evaluate its effectiveness following prior immunotherapy. ^{2 4 6 7 8}

Who Is on the Research Team?

Mercedes Porosnicu

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39869839/

Correlates of Cetuximab Efficacy in Recurrent and ... Results: We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2745918/

The Role of Cetuximab for the Treatment of Squamous Cell ... Cetuximab is an active drug in head and neck cancer, with randomized trial evidence that it improves survival when given with radiotherapy or cisplatin ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0802656

Platinum-Based Chemotherapy plus Cetuximab in Head ... Cetuximab is effective in recurrent or metastatic squamous-cell carcinoma of the head and neck that progresses despite platinum-containing therapy.

4. news.bms.com news.bms.com/news/details/2008/ERBITUXR-Five-Year-Data-Show-Significant-Improvement-in-Overall-Survival-for-Patients-with-Locally-or-Regionally-Advanced-Head-and-Neck-Cancer/default.aspx

ERBITUX(R) Five-Year Data Show Significant ... These five-year data demonstrate that the addition of ERBITUX to radiation therapy resulted in a significant increase in median overall survival for patients ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10440-7

Treatment outcomes of cetuximab-containing regimen in ... SCCHN with locoregional recurrence is associated with better disease control and survival outcomes comparing to distant metastatic SCCHN when treated with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33751752/

Safety and Efficacy of Cetuximab-Based Salvage ... Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00122460

Study Details | NCT00122460 | Cetuximab (Erbitux) in ... The purpose of this trial is to investigate the efficacy of cetuximab in combination with chemotherapy in comparison to chemotherapy alone in patients with ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf

ERBITUX (cetuximab) - accessdata.fda.gov The most common adverse reactions in ERBITUX clinical trials (incidence ≥25%) include cutaneous adverse reactions. (including rash, pruritus, and nail changes), ...