Cetuximab + Nivolumab for Head and Neck Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Nasopharynx cancer, Salivary gland cancer, others

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

Compensation: Varies

Number of Visits: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two cancer treatments, Cetuximab (a monoclonal antibody) and Nivolumab (an immunotherapy drug), benefits people with advanced head and neck cancer. Both drugs have approval for use, but the study tests whether their combination is more effective. Individuals with squamous cell carcinoma in areas such as the mouth, throat, or sinuses, who have not responded to other treatments, may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group.

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 have had chemotherapy, biological therapy, or radiation within 4 weeks before joining the study, and you must not be on certain immunosuppressive medications within 14 days of starting the trial.

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

A previous study found that the combination of cetuximab and nivolumab was generally well-tolerated by patients with recurring or spreading head and neck cancer. Research shows that common side effects include tiredness, skin reactions, and mild reactions during infusion, typical for these treatments. Serious side effects were less common but included immune-related issues, which could be managed with standard treatments.

Both cetuximab and nivolumab have FDA approval for treating head and neck cancer, indicating their safety when used separately. While their combination is still under study, the individual approval of these drugs provides some reassurance about their safety.

For concerns about specific side effects or their impact, discussing them with a healthcare provider is important. They can help weigh the potential benefits against any risks based on personal health situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cetuximab and Nivolumab for head and neck cancer because it offers a unique dual approach. Unlike standard treatments, which often involve surgery, radiation, or chemotherapy, Cetuximab is an antibody that targets the epidermal growth factor receptor (EGFR) on cancer cells, potentially inhibiting their growth. Nivolumab is an immune checkpoint inhibitor that helps unleash the body’s immune system to attack cancer cells. This combination could enhance the body's ability to fight cancer more effectively, offering hope for better outcomes compared to existing therapies.

What evidence suggests that the combination of Cetuximab and Nivolumab could be effective for head and neck cancer?

Research has shown that combining cetuximab and nivolumab can help treat head and neck squamous cell carcinoma (HNSCC). This trial will evaluate the combination of these two drugs, testing different dosing strategies in separate treatment arms. Studies indicate that this combination is safe and can extend survival, particularly for patients whose cancer has recurred or metastasized. Cetuximab blocks a protein that promotes cancer cell growth, while nivolumab enhances the immune system's ability to fight cancer. Patients who have used these drugs have demonstrated positive outcomes, even when other treatments failed. This evidence suggests that using both cetuximab and nivolumab together could benefit individuals with advanced HNSCC. ^{2 3 5 6 7}

Who Is on the Research Team?

Christine H. Chung, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Adults with advanced Head and Neck Squamous Cell Carcinoma (HNSCC) who have already tried at least one treatment like chemotherapy or radiation. They must be in good enough health to participate, not pregnant, and using effective contraception if sexually active. People can't join if they've had certain recent treatments, uncontrolled illnesses, severe allergies to similar drugs, or specific heart conditions.

Inclusion Criteria

Participants must have a life expectancy of greater than 3 months

My cancer is confirmed as squamous cell carcinoma in the specified areas.

Participants, if sexually active, must meet contraceptive requirements

Exclusion Criteria

I had severe skin reactions from previous EGFR therapy.

My cancer is p16 negative and started in the lymph nodes of my neck.

I had a severe reaction to previous anti-PD1 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive cetuximab and nivolumab every 2 weeks for 12 cycles or until discontinuation. Dose limiting toxicity assessment during Cycle 1.

48 weeks

12 visits (in-person)

Phase II Treatment

Participants receive cetuximab and nivolumab at the recommended Phase II dose.

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Imaging studies every 8 weeks during Cycle 1-6 and every 12 weeks during Cycle 7-12.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Nivolumab

Trial Overview The trial is testing the effectiveness of combining two FDA-approved cancer drugs—Cetuximab and Nivolumab—in treating HNSCC. Researchers want to see if this drug duo works better together for patients whose cancer has returned or spread and cannot be cured with surgery or radiation alone.

How Is the Trial Designed?

Group I: Phase II - Moffitt Site Only Experimental Treatment 2 Interventions

Nivolumab and Cetuximab at recommended Phase II dose (RP2D).

Group II: Phase II - Affiliate Sites Only Experimental Treatment 2 Interventions

Nivolumab and Cetuximab at recommended Phase II dose (RP2D).

Group III: Phase I - Moffitt Site Only Experimental Treatment 2 Interventions

Nivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m\^2; Nivolumab 240 mg.

Group IV: Phase I - Affiliate Sites Only Experimental Treatment 2 Interventions

Nivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m\^2; Nivolumab 240 mg.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

James and Esther King Biomedical Research Program

Collaborator

Trials

15

Recruited

2,200+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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]

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]

Cétuximab, a monoclonal antibody targeting EGFR, has been shown to improve overall survival in patients with locally advanced head and neck cancer when used alongside radiotherapy, and is now reimbursed in Belgium under specific conditions.

In metastatic head and neck cancer, adding cétuximab to platinum-based chemotherapy has demonstrated improved overall survival compared to chemotherapy alone, marking a significant advancement in treatment options, although it is not yet available to Belgian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monoclonal antibodies for the treatment of head and neck cancer]. Sautois, B., Martin, M., Demez, P., et al.[2018]

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]

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, an EGFR-inhibiting antibody used for treating certain cancers, is generally considered safe and well-tolerated, but this case highlights the potential for severe complications following its use, particularly in complex surgical situations.

The patient experienced a rare and fatal combination of complications after surgery, raising concerns about the safety of cetuximab in the context of surgical procedures, and emphasizing the need for careful monitoring and documentation of adverse effects in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. Knauer, M., Haid, A., Ammann, K., 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]

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]

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, 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7967147/

Concurrent Cetuximab and Nivolumab as a Second-Line ... To improve overall survival (OS), we evaluated a combination of cetuximab and nivolumab for toxicity and efficacy in patients with incurable ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.6017

Efficacy of concurrent cetuximab (CTX) and nivolumab ... Our data indicate the combination of CTX and NIVO is safe and effective in pts with previously untreated incurable R/M HNSCC.

3. opdivo.com opdivo.com/head-and-neck-cancer/clinical-trial-results

Clinical trial results for previously treated head and neck ... See how OPDIVO® (nivolumab) performed in clinical trials for certain adults with previously treated squamous cell head and neck cancer (SCCHN).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03370276

Study Details | NCT03370276 | Cetuximab & Nivolumab in ... The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in participants with Head and Neck ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8134300/

Effectiveness of nivolumab affected by prior cetuximab use ... Conclusions. These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.6010

RTOG 3504. | Journal of Clinical Oncology This trial evaluates the safety of adding nivo to 4 standard radiotherapy (RT) regimens for pts with newly diagnosed IR/HR HNSCC (Table). Safety ...

7. asco.org asco.org/videos-slides/VIDEOSANDSLIDES160234

Safety evaluation of nivolumab (Nivo) concomitant with ... Safety evaluation of nivolumab (Nivo) concomitant with cetuximab-radiotherapy for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck ...