Radiation Therapy + Cetuximab for Head and Neck Cancer

Not currently recruiting at 276 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: Anti-EGF therapy

Disqualifiers: Prior invasive malignancy, AIDS, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether radiation therapy alone or combined with cetuximab, a drug that blocks tumor growth, is more effective for patients who have undergone surgery for locally advanced head and neck cancer. Researchers seek to assess if 3-D imaging can focus radiation to kill more cancer cells while reducing side effects. Patients who have had surgery to remove a head or neck tumor and possess certain risk factors, such as cancer spreading to nearby nerves or blood vessels, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that cetuximab, when combined with radiation therapy, yields promising results for treating head and neck cancer. Studies have found that adding cetuximab to radiation or chemotherapy can improve survival rates. Cetuximab is generally well-tolerated, though some individuals might experience side effects such as skin reactions, low magnesium levels, or allergic reactions, which are usually manageable.

The safety of intensity-modulated radiation therapy (IMRT) is also well-documented. IMRT targets cancer cells more precisely, potentially reducing side effects compared to older radiation methods. Overall, both treatments are considered fairly safe for patients, though, like all treatments, they can carry some risks. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for head and neck cancer?

Researchers are excited about combining intensity-modulated radiation therapy (IMRT) with cetuximab for head and neck cancer because it offers a unique approach compared to standard treatments like surgery, radiation alone, or chemotherapy. Cetuximab is an antibody that targets the epidermal growth factor receptor (EGFR), which is often overexpressed in head and neck cancers, helping to inhibit tumor growth. Adding cetuximab to IMRT could enhance the effectiveness of radiation by making cancer cells more sensitive to it, potentially leading to better outcomes without the increased toxicity associated with traditional chemotherapy. This combination aims to provide a more targeted attack on cancer cells while sparing healthy tissue, offering a promising alternative for patients.

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

This trial will compare the effects of radiation therapy alone to radiation therapy combined with cetuximab for patients with head and neck cancer. Studies have shown that adding cetuximab to radiation therapy can improve outcomes for these patients. Specifically, research indicates that cetuximab, when combined with radiation, significantly increases survival rates. This approach leverages cetuximab's ability to block tumor growth and target cancer cells more effectively. Additionally, evidence suggests that cetuximab is particularly effective for patients who have not responded well to other treatments. Overall, cetuximab with radiation therapy offers a promising option for improving treatment success in head and neck cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Mitchell Machtay, MD

Principal Investigator

Milton S. Hershey Medical Center, Penn State Health

Are You a Good Fit for This Trial?

This trial is for individuals who've had surgery for locally advanced head and neck cancer, specifically squamous cell carcinoma. They should be in the early stages of the disease (T1, N1-2, M0 or T2-4a, N0-2, M0) and have 'intermediate' risk of recurrence. People with a history of other cancers within 5 years (except certain skin cancers), lymphoproliferative disorders, or living outside the US cannot participate.

Inclusion Criteria

I had surgery to remove my tumor completely within the last 7 weeks, aiming for a cure.

I have been diagnosed with squamous cell carcinoma in the head or neck.

My cancer is in an early stage but may have spread to nearby lymph nodes.

Exclusion Criteria

I have had a condition where my lymphocytes grow abnormally.

I haven't had cancer in the last 5 years, except for skin cancer.

I have a history of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks

6 weeks

5 visits per week (in-person)

Cetuximab Administration

Participants receive cetuximab IV once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT

11 weeks

1 visit per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

1 visit at 1 month, 1 visit at 3 months, every 3 months for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Intensity-Modulated Radiation Therapy

Trial Overview The study is examining if adding cetuximab to intensity-modulated radiation therapy (IMRT) improves outcomes compared to IMRT alone after surgery. It's a phase III trial where patients are randomly assigned to either receive radiation only or radiation plus cetuximab.

How Is the Trial Designed?

Group I: Arm II: IMRT plus cetuximab Experimental Treatment 2 Interventions

Radiation therapy (RT): 60 Gy IMRT, 2 Gy/day in 30 fractions (5 days a week for 6 weeks). Cetuximab: 400 mg/m\^2 intravenously (IV) at least 5 days prior to IMRT; 250 mg/m\^2 IV once a week for 6 weeks during RT and continuing 4 weeks after RT.

Group II: Arm I: Intensity-Modulated Radiotherapy Active Control 1 Intervention

Radiation therapy: 60 Gy intensity-modulated radiotherapy (IMRT), 2 Gy/day in 30 fractions (5 days a week for 6 weeks).

Intensity-Modulated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in European Union as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in Canada as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Who Is Running the Clinical Trial?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

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]

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]

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

Correlates of Cetuximab Efficacy in Recurrent and ... Cetuximab-based therapy shows limited efficacy in R/M HNSCC post-ICI, although outcomes were better in virus-independent HNSCC and ...

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. ascopubs.org ascopubs.org/doi/10.1200/GO.24.00059

Efficacy and Safety of Biosimilar Cetuximab Versus ... This trial compared the efficacy and safety of biosimilar cetuximab versus innovator cetuximab (IC) in combination with platinum-based chemotherapy in patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11925625/

Practical Consensus Guidelines on the Use of Cetuximab in ... Treatment sequences in patients with recurrent or metastatic head and neck squamous cell carcinoma: cetuximab followed by immunotherapy or vice versa.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842821002122

Cetuximab in locally advanced head and neck squamous ... This review focuses on the mechanisms of action of cetuximab, highlighting, in particular, the consequences of the binding to EGFR, and the pathways involved ...