Radiation Therapy + Immunotherapy for Head and Neck Cancer

No longer recruiting at 281 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants

Disqualifiers: Prior malignancy, Prior radiotherapy, Prior immunotherapy, Major surgery, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: 7-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining radiation therapy with either durvalumab or cetuximab is more effective in treating head and neck cancer that has spread locally. Radiation therapy uses high-energy x-rays to kill cancer cells, while durvalumab and cetuximab help the immune system fight cancer or prevent tumor growth. The trial compares these two combinations to determine which is more effective. It may suit those with head and neck cancer that has not spread far from its original location and who cannot use the common treatment, cisplatin, due to medical reasons like kidney issues or hearing loss. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research shows that cetuximab, when combined with radiation therapy, has been safely used in patients with head and neck cancer. Studies indicate that adding cetuximab to radiation can extend patient survival, making it a well-tolerated option. Like any treatment, it can have side effects, but these are usually manageable and expected in cancer care.

Research has also found durvalumab to be safe for head and neck cancer patients, with safety similar to other treatments of its kind. Patients have shown early and lasting positive responses, and the side effects are generally manageable.

Both treatments have been tested in various studies and show promise in treating head and neck cancer with manageable safety profiles. Participants should discuss potential risks and benefits with their healthcare providers to make informed decisions about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they offer innovative approaches by combining radiation therapy with immunotherapy agents. Unlike traditional treatments like chemotherapy, which directly attack cancer cells, these therapies harness the body's immune system to enhance cancer-fighting capabilities. In Arm I, cetuximab is used, an antibody that targets the epidermal growth factor receptor (EGFR) on cancer cells, potentially improving the effectiveness of radiation therapy. Arm II features durvalumab, a checkpoint inhibitor that blocks the PD-L1 protein, allowing immune cells to better recognize and attack cancer cells. These therapies could provide more precise and powerful options with potentially fewer side effects than conventional treatments.

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

Research has shown that combining cetuximab with radiation therapy can significantly improve survival rates for people with head and neck cancer. Studies have found it effective in controlling the disease when the cancer returns in nearby areas. In this trial, one group of participants will receive cetuximab with radiation therapy, which past trials have shown to better control the disease compared to other treatments.

Another group in this trial will receive durvalumab, a type of immunotherapy, alongside radiation therapy. Early studies indicate that durvalumab can lead to lasting improvements in patients who have already undergone many treatments. The safety of durvalumab is considered manageable, and evidence suggests it helps the immune system attack cancer cells. Both treatments are being studied in this trial for their potential to enhance the effectiveness of radiation therapy in fighting head and neck cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Loren K Mell

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced head and neck cancer who can't use cisplatin. They must have untreated, unresected squamous cell carcinoma in specific regions (larynx, hypopharynx, oropharynx, oral cavity) and meet health criteria like blood counts and organ function tests. Pregnant women are excluded, as are those with recent cancers (except certain skin/prostate cancers), severe illnesses or allergies to the drugs tested.

Inclusion Criteria

I am not pregnant and meet the criteria for being post-menopausal if applicable.

I have advanced cancer in my head or neck area.

I have submitted tissue samples for review and analysis to UCSF.

Exclusion Criteria

I haven't had cancer (except skin or early prostate cancer) in the last 3 years.

I need help with my personal care and cannot do any physical work.

My body weight is 30 kg or less.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either cetuximab or durvalumab with concurrent radiation therapy

7-8 weeks

Weekly visits for radiation therapy and cetuximab; every 4 weeks for durvalumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

4.2 years

1 month post-treatment, then every 4 months for 1 year, every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Durvalumab
• Intensity-Modulated Radiation Therapy

Trial Overview The study compares radiation therapy combined with durvalumab (an immunotherapy drug) versus cetuximab (another type of monoclonal antibody). It aims to see which combination works better for shrinking tumors in patients who cannot take cisplatin.

How Is the Trial Designed?

Group I: Arm II (durvalumab, radiation therapy) Experimental Treatment 5 Interventions

Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

Group II: Arm I (cetuximab, radiation therapy) Active Control 5 Interventions

Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

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]

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]

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]

The recommended phase II dose (RP2D) of ipilimumab, when added to standard cetuximab and radiotherapy for high-risk head and neck squamous carcinoma, is established at 1 mg/kg, demonstrating a tolerable safety profile with manageable adverse effects.

The combination treatment resulted in a promising 3-year disease-free survival and overall survival rate of 72%, indicating its efficacy without the need for cytotoxic chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. Ferris, RL., Moskovitz, J., Kunning, S., 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]

Citations

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

Correlates of Cetuximab Efficacy in Recurrent and ... Results: We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33751752/

Safety and Efficacy of Cetuximab-Based Salvage ... Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25904751/

Safety and Tumor Specificity of Cetuximab-IRDye800 for ... Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00122460

Study Details | NCT00122460 | Cetuximab (Erbitux) in ... The purpose of this trial is to investigate the efficacy of cetuximab in combination with chemotherapy in comparison to chemotherapy alone in patients with ...