Imatinib + Cetuximab for Head and Neck Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Investigational agents

Disqualifiers: Nasopharyngeal carcinoma, Uncontrolled diabetes, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1-2 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, imatinib and cetuximab, in patients with head and neck cancer who are about to undergo surgery or radiation. Researchers want to see if a specific protein in the tumor cells affects how well the treatment works. Participants will be involved in the study for over a year. Imatinib has been used for several years in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you've had chemotherapy or radiotherapy within 4 weeks before the study, or if you're on other investigational drugs.

Is the combination of Imatinib and Cetuximab safe for humans?

Cetuximab has been used safely in humans for conditions like colorectal cancer and head and neck cancer, but it can cause side effects like skin reactions. The safety of combining it with Imatinib specifically for head and neck cancer isn't detailed here, but both drugs have been used in humans for other conditions. ^{1 2 3 4 5}

What makes the drug combination of Imatinib and Cetuximab unique for head and neck cancer?

The combination of Imatinib and Cetuximab is unique for head and neck cancer because Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), has shown improved survival when added to radiotherapy in this cancer type, and the combination with Imatinib may offer a novel approach to enhance treatment efficacy. ^{1 6 7 8 9}

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

Cetuximab, a drug that targets the epidermal growth factor receptor (EGFR), has been approved for use in head and neck squamous cell carcinoma (HNSCC) since 2006, showing effectiveness in treating this type of cancer. Additionally, cetuximab has shown positive responses in treating squamous cell skin cancer, suggesting its potential benefit in similar cancer types. ^{1 4 10 11 12}

Who Is on the Research Team?

Justine Bruce, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Adults over 18 with squamous cell carcinoma of the head and neck, who are candidates for curative surgery or chemoradiation. They must have a tumor large enough for biopsy samples and adequate organ function. Excluded are those with certain other cancers, recent major treatments, ongoing investigational drug use, allergies to study drugs, or severe medical conditions.

Inclusion Criteria

I am a candidate for treatment aimed at curing my cancer through surgery, radiation, or both.

My tumor is large enough for multiple biopsy samples after treatment.

My oropharyngeal cancer is HPV-negative.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 to 6 weeks.

Subjects who are receiving any other investigational agents

I do not have any severe illnesses that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive two doses of cetuximab and a course of imatinib for 8 to 14 days prior to definitive surgery or radiation

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for hospital re-admissions and adverse events

28 days

Long-term follow-up

Participants are monitored for changes in Ki67 index and adverse events related to the treatment

6 months to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Imatinib

Trial Overview This trial tests if protein AXL levels in tumors predict response to cetuximab combined with imatinib in head and neck cancer patients. Participants will be studied from diagnosis until up to 16 months after treatment involving surgery or chemoradiation.

How Is the Trial Designed?

Group I: Imatinib Cetuximab Combination Experimental Treatment 2 Interventions

Participants will receive two doses of CTX and a minimum of an 8 day (maximum 14 day) course of imatinib prior to definitive surgery or definitive radiation/chemoradiation.

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?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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, 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]

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]

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]

Adding the EGFR inhibitor cetuximab to radiotherapy for locally advanced squamous cell carcinoma of the head and neck significantly improves clinical outcomes without increasing the toxicity associated with radiotherapy.

Current chemoradiotherapy regimens, which are often platinum-based, have reached a limit in tolerable toxicity, highlighting the need for more effective and tolerable treatment options like cetuximab combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? Bernier, J., Schneider, D.[2015]

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]

The combination treatment of carboplatin, 5-FU, and cetuximab with intensity-modulated radiation therapy (IMRT) showed promising efficacy in treating locally advanced squamous cell carcinoma of the head and neck, with a complete response rate of 28.6% at the first follow-up and 92.9% thereafter.

While the treatment was associated with moderate toxicity, including significant skin reactions and mucositis, these side effects were manageable and resolved quickly, indicating that the regimen is feasible for routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiochemoimmunotherapy with intensity-modulated concomitant boost: interim analysis of the REACH trial. Jensen, AD., Krauss, J., Potthoff, K., et al.[2023]

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]

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]

Citations

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

Cetuximab. [2020]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? [2015]

9. England pubmed.ncbi.nlm.nih.gov

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

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

Radiochemoimmunotherapy with intensity-modulated concomitant boost: interim analysis of the REACH trial. [2023]

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

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

12. 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]