Cetuximab + Afatinib for Head and Neck Cancer

Overseen By Cindy Voghell

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Erlotinib, Gefitinib, Lapatinib, others

Disqualifiers: Brain metastases, Interstitial lung 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking certain medications before starting the study treatment. If you are on medications that are not allowed during the trial, you may need to stop them. It's best to discuss your current medications with the trial team to see if any changes are needed.

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

Research shows that Cetuximab, when combined with chemotherapy or radiotherapy, has shown modest effectiveness in treating advanced squamous cell carcinoma of the head and neck. Additionally, Cetuximab is used in chemoradiation therapy for locally advanced head and neck cancer, indicating its role in treatment strategies. ^{1 2 3 4 5}

Is the combination of Cetuximab and Afatinib safe for head and neck cancer patients?

Cetuximab, when used with radiation therapy, can increase the risk of serious skin reactions (dermatitis) in head and neck cancer patients. Combining cetuximab with other treatments may also lead to increased toxicity, especially in patients with other health issues. ^{2 6 7 8 9}

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

The combination of Cetuximab and Afatinib is unique because Cetuximab targets the epidermal growth factor receptor (EGFR), which is often overexpressed in head and neck cancers, potentially enhancing the effectiveness of chemotherapy and radiotherapy. Afatinib, another EGFR inhibitor, may work synergistically with Cetuximab to improve outcomes by further blocking cancer cell growth and survival pathways. ^{1 3 4 10 11}

Research Team

Aarti Bhatia, MD, MPH

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults with advanced squamous cell carcinoma of the head and neck that has returned or spread after platinum-based chemotherapy or immune checkpoint inhibitor treatment. Participants must have measurable disease, be in a stable condition (ECOG ≤2), and have proper organ function. Pregnant women, those with certain allergies, untreated viral hepatitis or HIV, recent radiotherapy recipients, and individuals on prohibited medications are excluded.

Inclusion Criteria

My cancer got worse within 6 months after finishing platinum-based treatment.

Adequate organ function including Hemoglobin ≥ 8 g/dl, ANC ≥1000 / mm3, Platelet count ≥75,000 / mm3, Estimated creatinine clearance > 45ml / min, Total Bilirubin ≤ 1.5 times upper limit of normal, AST or ALT ≤ three times the upper limit of normal, Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines, Negative urine or serum pregnancy test for women of childbearing potential

My cancer in the head or neck area is advanced and cannot be cured with surgery or radiation.

Exclusion Criteria

I have a serious lung condition affecting the tissue and space around the air sacs.

I have untreated viral hepatitis or HIV.

I have completed treatment for brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly/bi-weekly intravenous cetuximab and daily oral afatinib until disease progression or development of Grade 3 or higher drug-related toxicities

Up to 2 years

Weekly/bi-weekly visits for cetuximab administration

Follow-up

Participants are monitored for overall survival and progression-free survival

1 year

Monthly phone calls

Treatment Details

Interventions

• Afatinib
• Cetuximab

Trial Overview The study tests combining two drugs—cetuximab and afatinib—to treat recurrent or metastatic head and neck cancer. It's a Phase II trial to see how effective this drug duo is when other treatments like chemo haven't worked.

Participant Groups

Group I: All subjects Experimental Treatment 2 Interventions

Advanced squamous cell carcinoma of the head and neck region, having previously been treated on a platinum based regimen or with an immune checkpoint inhibitor. Subjects will receive Afatinib dose 30 mg per day and weekly/bi-weekly intravenous cetuximab.

Afatinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Gilotrif for:

• Non-small cell lung cancer

Approved in European Union as Giotrif for:

• Non-small cell lung cancer

Approved in Canada as Gilotrif for:

• Non-small cell lung cancer

Approved in Japan as Giotrif for:

• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Findings from Research

Cetuximab, an epidermal growth factor receptor inhibitor, shows promise in treating advanced squamous cell carcinoma of the head and neck due to the common expression of this protein in tumors.

Clinical trials indicate that cetuximab has modest effectiveness when used alongside chemotherapy or radiotherapy, suggesting it can be a valuable addition to treatment regimens for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cetuximab in combination with radiotherapy or chemotherapy against advanced squamous cell carcinoma of the head and neck. Li, JZ., Zheng, JW., Zhang, ZY.[2019]

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 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]

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]

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 180 patients with head and neck cancer, those treated with cetuximab experienced significantly higher rates of acute dermal toxicity (34.5%) compared to those who did not receive cetuximab (10.3%).

Despite the increased skin toxicity, there were no significant differences in local control or overall survival between patients treated with cetuximab and those treated without it, indicating that cetuximab does not improve survival outcomes when combined with IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. Bibault, JE., Morelle, M., Perrier, L., et al.[2022]

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]

Cetuximab is a monoclonal antibody that effectively inhibits the epidermal growth factor receptor (EGFR), which plays a crucial role in tumor growth and resistance to treatments like chemotherapy and radiotherapy.

Clinical data suggest that cetuximab not only has its own anticancer effects but may also enhance the effectiveness of chemotherapy and radiotherapy in patients with advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. Merlano, M., Occelli, M.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

Evaluation of Cetuximab in combination with radiotherapy or chemotherapy against advanced squamous cell carcinoma of the head and neck. [2019]

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

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

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. 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]

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

Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K521 Polymorphism. [2023]

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. England pubmed.ncbi.nlm.nih.gov

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. [2023]

8. Cyprus pubmed.ncbi.nlm.nih.gov

The efficacy of combined treatment with cetuximab (erbitux) and radiation therapy in patients with head and neck cancer. [2018]

9. France pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. [2021]