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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a protein called AXL in tumor cells affects the response to a combination of two drugs, cetuximab (a targeted therapy) and imatinib (a type of cancer drug), in treating head and neck cancer. The researchers aim to determine if these drugs together can be effective before surgery or other major treatments. Participants should have squamous cell carcinoma in the head or neck and be prepared for curative treatments like surgery or radiation. Eligible participants will undergo blood draws and biopsies over approximately 13 to 16 months. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining the drugs imatinib and cetuximab has been tested for treating head and neck cancer. In earlier studies, patients took these drugs but experienced some side effects. For example, in one study with 24 patients, five saw their cancer shrink, and six had their cancer remain the same size.

While these results are encouraging, the combination can cause side effects like skin reactions or tiredness. This combination remains in the early stages of testing, so more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which often include surgery, radiation, and traditional chemotherapy, the combination of Imatinib and Cetuximab offers a unique approach. Imatinib targets specific proteins within cancer cells, potentially interrupting their growth signals, while Cetuximab is an antibody that blocks a key receptor involved in cancer cell proliferation. Researchers are excited because this combination could provide a more targeted attack on cancer cells, potentially leading to better outcomes with fewer side effects compared to conventional therapies. Additionally, this treatment might be effective in a shorter time frame, showing promise before surgery or radiation even begins.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that cetuximab can treat head and neck cancer by targeting a protein called EGFR, often found on cancer cells. Some patients with this cancer type have responded well to cetuximab, with their disease remaining stable. Imatinib targets different proteins that aid cancer cell growth. In this trial, participants will receive a combination of cetuximab and imatinib to evaluate whether using them together enhances treatment effectiveness, as they may work synergistically against cancer cells. Early results suggest this combination could be promising, but further research is needed to fully understand its benefits. ^{1 3 5 6 7}

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

History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or CTX

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

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]

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]

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 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]

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 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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/imatinib-cetuximab-for-head-and-neck-cancer-7c807

Imatinib + Cetuximab for Head and Neck Cancer 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.

2. esmed.org esmed.org/MRA/index.php/mra/article/download/77/45

THE RATIONALE FOR COMBINATION THERAPIES Here, we will use head and neck squamous cell carcinoma as a model for genetically complex disease and discuss novel approaches to enhance personalized medicine ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5328630/

A review of drugs in development for the personalized ... For instance, although cetuximab has shown efficacy in head and neck cancer, gefitinib (a tyrosine kinase inhibitor also targeting EGFR) has not shown any ...

4. mdpi.com mdpi.com/2072-6694/12/11/3381

Outcome of Targeted Therapy Recommendations for ... Eventually, 14 patients (28%) received the suggested targeted therapy. Six of fourteen patients (43%) achieved stable disease conditions and four patients (29%) ...

5. nature.com nature.com/articles/s41392-024-01856-7

Exploring treatment options in cancer: tumor ... The use of these drugs has been associated with improved outcomes in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6771657/

A phase 1b study evaluating the safety and pharmacokinetics ... Of the 24 patients included in the efficacy analysis, five patients achieved a partial response (PR; 21%), six had stable disease (25%) and 13 had progressive ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842818304967

Target therapies in recurrent or metastatic head and neck ... Recurrent or metastatic head and neck squamous-cell carcinomas (R/M HNSCC) are a group of cancers with a very poor prognosis. Many clinical trials testing ...