Chemotherapy + Radiation Therapy for Head and Neck Cancer

Recruiting at287 trial locations

Overseen by Paul M Harari

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to compare the usual treatment (radiation therapy with cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy, and using the usual treatment plus an immunotherapy drug, atezolizumab.

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.

What data supports the effectiveness of the treatment for head and neck cancer?

Research shows that combining cetuximab with intensity-modulated radiation therapy (IMRT) is more effective than using radiation alone for head and neck cancer. Additionally, using cetuximab with docetaxel and cisplatin has shown promising results in treating recurrent or metastatic head and neck cancer. ^{1 2 3 4 5}

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

The combination of cetuximab with intensity-modulated radiation therapy (IMRT) for head and neck cancer has been studied, showing some serious skin reactions (dermatitis) and other severe side effects like neutropenia (low white blood cell count) when combined with other drugs like docetaxel and cisplatin. However, cetuximab with radiotherapy alone has shown benefits without increasing radiation-related side effects. ^{1 2 3 6 7}

What makes the chemotherapy and radiation treatment for head and neck cancer unique?

This treatment combines chemotherapy drugs (cetuximab, cisplatin, and docetaxel) with intensity-modulated radiation therapy (IMRT), which allows for precise targeting of cancer cells while sparing healthy tissue. Cetuximab, an antibody that targets the EGFR protein on cancer cells, enhances the effectiveness of radiation, making this combination potentially more effective than traditional chemotherapy and radiation alone. ^{1 3 8 9 10}

Research Team

Paul M Harari

Principal Investigator

NRG Oncology

Eligibility Criteria

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

I am 18 years old or older.

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

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

Trial Timeline

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

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Cetuximab (Monoclonal Antibodies)
• Cisplatin (Platinum-containing Compound)
• Docetaxel (Taxane)
• Intensity-Modulated Radiation Therapy (Radiation)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. 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]

2. United States 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. [2018]

3. Germany 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2022]

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. England 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? [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced head and neck cancer: a feasibility study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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