Chemotherapy + Radiation Therapy for Head and Neck Cancer

Recruiting at 342 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Anti-PD-1 agents

Disqualifiers: Prior invasive malignancy, Severe cardiac disease, Severe infections, Autoimmune disease, 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: 6

Duration: 6 weeks

613 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best combination of treatments for high-risk stage III-IV head and neck cancer, specifically squamous cell carcinoma. Researchers are examining the effectiveness of radiation therapy alone and in combination with chemotherapy drugs like cisplatin, docetaxel, cetuximab, and the immunotherapy drug atezolizumab. Individuals who have undergone surgery to remove their cancer and possess certain high-risk features, such as cancer reaching the edge of the removed tissue, might be suitable candidates. This study could enhance cancer treatment by potentially reducing side effects through more precise targeting. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in cancer care.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving certain immunosuppressive medications or those with severe co-morbidities may be excluded, so it's best to discuss your specific medications with the trial team.

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

Research shows that combining radiation therapy with cisplatin is generally well-tolerated for head and neck cancer, with manageable side effects. While some patients may experience severe skin or mouth issues, these are uncommon.

For those receiving docetaxel with radiation, severe side effects like skin irritation and mouth sores have been reported, but they occur in only a small number of patients.

Studies have shown that adding cetuximab (a type of targeted therapy) to docetaxel and radiation can improve survival rates. Although this combination can enhance treatment effectiveness, it may also increase the risk of side effects.

When cisplatin is combined with atezolizumab (an immunotherapy drug), research indicates it is generally safe. Atezolizumab aids the immune system in attacking cancer cells and can be effective with fewer severe side effects compared to traditional treatments.

Overall, these combinations have been studied to ensure they are as safe as possible while providing effective treatment options for head and neck cancer. ^{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 explore innovative combinations and strategies. Unlike the standard of care that typically involves surgery, radiation, and chemotherapy, these investigational treatments combine intensity-modulated radiation therapy (IMRT) with different chemotherapy drugs like cisplatin, docetaxel, and cetuximab, and even include an immunotherapy drug, atezolizumab, in one arm. Atezolizumab is particularly intriguing as it harnesses the body's immune system to target cancer cells, offering a different mechanism of action compared to traditional treatments. These combinations aim to enhance effectiveness and potentially reduce side effects by targeting the cancer more precisely, which could lead to better patient outcomes.

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

Studies have shown that combining radiation therapy with the drug cisplatin effectively treats head and neck cancer. Research indicates that this combination can help control tumors and improve survival rates. In this trial, one group of participants will receive this combination. Another group will receive radiation therapy with docetaxel, which has also improved survival compared to radiation alone. A separate group will receive radiation, docetaxel, and cetuximab, which can further increase overall survival by inhibiting cancer cell growth. Additionally, a different group will receive atezolizumab, an immunotherapy, combined with radiation and cisplatin, which can enhance the body's immune response against cancer, potentially leading to better outcomes. This trial studies each treatment option to evaluate their effectiveness in improving cancer treatment. ^{1 6 7 8 9}

Who Is on the Research Team?

Paul M Harari

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with high-risk head and neck cancer who've had surgery to remove it. They should have no other cancers for the past 3 years, not be pregnant, and agree to birth control if needed. Key eligibility includes recent imaging tests, certain blood levels within normal ranges, a specific type of tumor (HNSCC), and good physical condition.

Inclusion Criteria

Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential

Assessments within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin

I agree to provide tissue samples for cancer analysis and have signed the study's consent form.

Exclusion Criteria

I have received chemotherapy or anti-EGF therapy for my cancer.

I have been cancer-free for at least 3 years, except for non-melanoma skin cancer.

Severe, active co-morbidity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intensity modulated radiation therapy (IMRT) and receive concurrent chemotherapy with cisplatin, docetaxel, cetuximab, or atezolizumab depending on the arm

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

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

Extension/Long-term follow-up

Participants may continue to be monitored for long-term outcomes and adverse events

Indefinite

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cetuximab
• Cisplatin
• Docetaxel
• Intensity-Modulated Radiation Therapy

Trial Overview The study compares usual treatment (radiation plus cisplatin) with radiation combined with docetaxel and cetuximab chemotherapy or adding atezolizumab immunotherapy. It aims to see which method is more effective in stopping cancer growth after surgery.

How Is the Trial Designed?

Group I: Arm 4 (IMRT, cisplatin, atezolizumab) Experimental Treatment 8 Interventions

Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.

Group II: Arm 3 (IMRT, docetaxel, cetuximab) Experimental Treatment 8 Interventions

Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.

Group III: Arm 2 (IMRT, docetaxel) Experimental Treatment 6 Interventions

Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)

Group IV: Arm 1 (IMRT, cisplatin) Experimental Treatment 7 Interventions

Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.

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+

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 43 patients with locally advanced head and neck cancer, combining radiotherapy with cisplatin and cetuximab, supported by amifostine, showed a high complete response rate of 68.5%, which increased to 77.2% with minor treatment delays.

The use of a high daily dose of amifostine (750-1,000 mg) was well tolerated by 41.8% of patients and was associated with fewer delays in radiotherapy, while the treatment was linked to a high incidence of acneiform rash but no severe amifostine-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced head and neck cancer: a feasibility study. Koukourakis, MI., Tsoutsou, PG., Karpouzis, A., et al.[2022]

The new chemotherapy regimen combining docetaxel, cisplatin, and cetuximab (B-CRT) for treating locally advanced head and neck squamous cell carcinoma resulted in severe neutropenia in 56% of patients, indicating significant safety concerns.

Due to the high incidence of adverse events, particularly neutropenia and leukopenia, the study was terminated early, and it remains unclear if B-CRT is as effective as the standard TPF-CRT regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. Nishimura, G., Taguchi, T., Takahashi, M., et al.[2018]

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]

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 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 TPEx regimen, which combines docetaxel, cisplatin, and cetuximab, achieved an objective response rate of 44.4% in 54 patients with recurrent or metastatic head and neck squamous cell carcinoma, indicating promising efficacy as a first-line treatment.

While the treatment was generally well-tolerated, notable adverse events included skin rash (16.6%) and non-febrile neutropenia (20.4%), with some serious complications leading to death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Guigay, J., Fayette, J., Dillies, AF., et al.[2022]

Cytotoxic chemotherapy for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) primarily includes platinum agents, taxanes, and antimetabolic agents, which are commonly used to manage the disease.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, shows modest effectiveness in treating R/M HNSCC, highlighting the importance of a multidisciplinary approach in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. Fury, MG., Pfister, DG.[2019]

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 combination of erlotinib and docetaxel with intensity-modulated radiotherapy (IMRT) showed promising efficacy in treating locally advanced head and neck squamous cell carcinoma, with a 3-year disease-free survival rate of 69.5% and overall survival rate of 81% based on a study of 43 patients over a median follow-up of 48.7 months.

The treatment was generally well-tolerated, although some patients experienced significant toxicities such as dysphagia, dermatitis, and mucositis, indicating that this regimen could be a viable option for patients who cannot tolerate cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of erlotinib and docetaxel with concurrent intensity-modulated radiotherapy in locally advanced head and neck squamous cell carcinoma. Yao, M., Woods, C., Lavertu, P., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3028434/

Comprehensive IMRT Plus Weekly Cisplatin for Advanced ... Comprehensive head and neck IMRT to 70 Gy delivered with weekly cisplatin chemotherapy (30 mg/m 2 ) is feasible and generally well tolerated.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3479880/

Clinical evaluation of intensity-modulated radiotherapy for ... Three centres have reported their experience of using IMRT to deliver TMI for SCCUP [64-66]. The 2-year locoregional control and overall survival were 85–88% ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00528

Cisplatin and Intensity-Modulated Radiation Therapy in ... Giving cisplatin and intensity-modulated radiation therapy may work better in treating patients with head and neck squamous cell carcinoma. Eligibility Criteria ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00265941

Study Details | NCT00265941 | Radiation Therapy and ... This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin.

6. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01966-4

safety propensity score analysis on 166 head and neck cancer ... Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for ...

7. nrgoncology.org nrgoncology.org/Home/News/Post/reduced-dose-radiation-with-cisplatin-improves-outcomes-for-hpv-associated-oropharyngeal-carcinoma-patients-on-nrg-oncology-study-justifies-phase-iii-trial

Reduced-Dose Radiation with Cisplatin Improves Outcomes f 2-year overall survival rates were 96.7% and 97.3% for the IMRT+C and the IMRT alone arms, respectively. While more grade 3-4 acute toxicities ...

8. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/imrt-matches-proton-therapy-in-patient-reported-outcomes-for

Intensity-modulated radiation therapy (IMRT) matches ... Survival rates were similarly high for both groups. At a median follow-up of 28.3 months, two-year freedom from cancer returning at or near the ...

9. mdpi.com mdpi.com/2072-6694/17/9/1444

Comparison of Weekly and Triweekly Cisplatin Regimens ... Overall, both schedules appear to be equally effective and safe. Our findings indicate that the treatment plan should be based on the individual patient's needs ...