Radiation Therapy + Cetuximab for Head and Neck Cancer

Recruiting at 263 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

702 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in treating patients who have undergone surgery for locally advanced head and neck cancer.

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.

What data supports the effectiveness of the treatment Radiation Therapy + Cetuximab for Head and Neck Cancer?

Research shows that combining cetuximab with intensity-modulated radiation therapy (IMRT) can be more effective than using radiation alone for treating head and neck cancer. Studies have found that this combination can improve local control of the cancer and overall survival rates compared to some other treatments. ^{1 2 3 4 5}

Is the combination of radiation therapy and cetuximab safe for head and neck cancer patients?

The combination of radiation therapy and cetuximab for head and neck cancer has been studied, and some patients experienced serious skin reactions (dermatitis) when treated with this combination. However, the studies primarily focus on the effectiveness and safety of this treatment for head and neck cancer, indicating that while there are side effects, it is generally considered safe for use in humans. ^{2 3 4 5 6}

How is the treatment of Radiation Therapy + Cetuximab for Head and Neck Cancer different from other treatments?

This treatment combines intensity-modulated radiation therapy (IMRT), which precisely targets cancer cells while sparing healthy tissue, with cetuximab, a drug that enhances the effects of radiation by targeting a specific protein on cancer cells. This combination is particularly beneficial for patients who cannot tolerate traditional chemotherapy. ^{1 2 3 5 7}

Research Team

Mitchell Machtay, MD

Principal Investigator

Milton S. Hershey Medical Center, Penn State Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

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

2. 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]

3. Japan pubmed.ncbi.nlm.nih.gov

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer. [2021]

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

Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Adjuvant therapy with cetuximab for locally advanced squamous cell carcinoma of the oropharynx: results from a randomized, phase II prospective trial. [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. Ireland pubmed.ncbi.nlm.nih.gov

Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: Results from a phase-I trial. [2020]