Reduced-Dose Radiotherapy for Head and Neck Cancer

(HN001 Trial)

Recruiting at 4 trial locations

Overseen By Song W

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Chemotherapy

Must not be taking: Antineoplastic drugs

Disqualifiers: Metastatic disease, Prior radiotherapy, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a lower dose of radiation therapy to determine its safety and effectiveness in treating squamous cell carcinoma in the head and neck area. The goal is to assess whether a reduced dose can remain effective while potentially causing fewer side effects. Participants are divided into groups, with some receiving chemotherapy alongside radiation, depending on their cancer's response. Suitable candidates for this trial include those diagnosed with squamous cell carcinoma in the oropharynx who plan to undergo radiation therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can receive concurrent systemic anticancer therapy and investigational agents with approval. 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?

A previous study found that using a lower dose of radiation for head and neck cancer was safe. This study showed that the reduced dose didn't increase the risk of cancer returning and decreased the chance of side effects. Another study confirmed that this lower-dose approach was as effective as the standard dose but caused fewer harmful effects on the body.

Adding chemotherapy to the reduced-dose radiation remained safe. Studies found that combining these treatments didn't worsen safety outcomes. Patients had similar survival rates whether they received chemotherapy weekly or every three weeks with the radiation.

Overall, research suggests that reduced-dose radiation, with or without chemotherapy, is safe and well-tolerated for patients with head and neck cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a reduced-dose radiotherapy approach for treating head and neck cancer, potentially minimizing side effects while maintaining effectiveness. Unlike standard treatments that typically involve higher radiation doses, these experimental protocols use a lower dose, which could lead to fewer long-term complications and better quality of life for patients. Additionally, the trial examines the impact of combining reduced-dose radiotherapy with chemotherapy, offering insights into whether this combination could enhance treatment efficacy, especially for those who don't respond rapidly. This innovative approach aims to refine treatment strategies, focusing on personalized care based on patient response.

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

This trial will evaluate reduced-dose radiotherapy for head and neck cancer across different treatment arms. Research has shown that a lower dose of radiation can be as effective as the usual higher dose, reducing the risk of long-term side effects. Participants in this trial may receive reduced-dose radiation either with or without concurrent chemotherapy. Studies have found that this approach does not affect the chances of cancer returning or survival rates. Specifically, for patients receiving both lower-dose radiation and chemotherapy, research indicates a survival benefit, making this combination promising. Other studies suggest that using less radiation with chemotherapy can lead to longer survival times. Overall, these methods aim to be effective while reducing harm. ^{1 2 3 6 7}

Who Is on the Research Team?

Chris McLaughlin, M.D.

Principal Investigator

UVA

Are You a Good Fit for This Trial?

This trial is for adults with HPV-positive squamous cell carcinoma of the oropharynx. They must be willing to use contraception, follow study procedures, and can receive other cancer treatments if approved. Excluded are those with distant metastasis, recent heart issues, severe infections or lung problems, liver dysfunction, AIDS, heavy tobacco history unless quit a year ago, current antineoplastic drug use for another cancer, prior head/neck radiation or another invasive malignancy within 3 years.

Inclusion Criteria

I am planning to undergo radiotherapy as my main or additional cancer treatment.

Provision of signed and dated informed consent form

I am able to get out of my bed or chair and move around.

Exclusion Criteria

Participant is a prisoner

Pregnancy or lactation

I do not have conditions like ataxia telangiectasia or scleroderma that prevent head and neck radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive a reduced dose of radiotherapy, with dosing determined by concurrent chemotherapy, HPV blood test results, physical exam, and imaging.

6-8 weeks

Routine visits for NavDx testing and treatment response assessment

Follow-up

Participants are monitored for safety, effectiveness, and disease progression after treatment

6 months to 1 year

Regular follow-up visits for safety and effectiveness evaluation

Long-term Follow-up

Participants are monitored for long-term survival and disease progression

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview

The trial tests a lower dose of radiation therapy on patients with head and neck squamous cell carcinomas to see if it's as effective and safer than standard doses. It includes people getting concurrent chemotherapy or immunotherapy for their condition.

How Is the Trial Designed?

Group I: Reduce Dose without Concurrent Chemotherapy Rapid Responder Experimental Treatment 1 Intervention

A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume.

Group II: Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder Experimental Treatment 1 Intervention

A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.

Group III: Reduce Dose with Concurrent Chemotherapy Rapid Responder Experimental Treatment 1 Intervention

A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume.

Group IV: Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder Experimental Treatment 1 Intervention

A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Intensity-modulated radiation therapy (IMRT) allows for higher doses of radiation to be delivered precisely to cancerous areas while minimizing exposure to surrounding healthy tissues, which can improve safety and reduce side effects.

IMRT is particularly beneficial for treating head and neck cancers due to the close proximity of tumors to critical structures, although there are concerns about the potential long-term risks of radiation exposure to non-target tissues, especially in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in the treatment of head and neck cancer. Eisbruch, A.[2018]

Recent advances in radiotherapy for head and neck cancer include improved techniques like three-dimensional conformal treatment planning and charged particle irradiation, which enhance targeting of tumors while minimizing damage to surrounding healthy tissue.

The review highlights the importance of combining radiotherapy with other treatments, such as neoadjuvant chemotherapy, to improve outcomes like laryngeal preservation and the effectiveness of postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in radiotherapy for head and neck cancer. Mendenhall, WM., Parsons, JT., Buatti, JM., et al.[2019]

Intraoperative radiotherapy is an effective method for delivering a higher radiation dose directly to tumors in head and neck carcinoma, which can improve local control of the disease.

This treatment is especially beneficial for patients with locally advanced head and neck lesions and for those experiencing recurrence of tumors that have not been previously irradiated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative radiotherapy of ORL cancers. Review of the literature]. Demange, L.[2006]

Intensity-modulated radiotherapy (IMRT) is a promising treatment for head and neck cancer as it effectively delivers high doses to tumors while minimizing damage to surrounding healthy tissues, which can improve patients' quality of life.

The article reviews current literature on IMRT's effectiveness across different subsites of head and neck cancer, highlighting its role in reducing side effects compared to traditional radiotherapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers. Bhide, SA., Newbold, KL., Harrington, KJ., et al.[2022]

In a study of 20 patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer, acute side effects were common, with 19 patients experiencing xerostomia (dry mouth) and 18 reporting mucositis (inflammation of the mucous membranes).

Long-term effects included persistent xerostomia in 11 out of 14 patients and an increase in trismus (restricted jaw movement) in 4 patients, indicating that while some acute symptoms improved, certain complications remained significant after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. Germano, F., Melone, P., Testi, D., et al.[2017]

Intensity-modulated radiation therapy (IMRT) allows for more precise radiation delivery in head and neck cancers, improving local control of tumors while minimizing damage to critical structures like the spine and parotid glands.

IMRT has been shown to preserve salivary function by sparing the parotid glands, although there are ongoing concerns about potential side effects, such as difficulties with swallowing and the risk of secondary cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for head and neck cancer. Caglar, HB., Allen, AM.[2007]

Intraoperative radiation therapy (IORT) shows promise as a treatment for locally advanced head and neck cancers, with a systematic review of 52 studies involving 2,389 patients indicating benefits in local control and manageable toxicity.

IORT is often used in conjunction with other treatments, particularly after salvage surgery for recurrent tumors, but more randomized trials are needed to compare its effectiveness against current standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of intraoperative radiation therapy for head and neck cancer. Villafuerte, CVL., Ylananb, AMD., Wong, HVT., et al.[2023]

Intensity Modulated Radiation Therapy (IMRT) combined with Image Guided Radiation Therapy (IGRT) enhances treatment for head and neck cancer by improving tumor coverage while minimizing damage to normal tissues, leading to similar tumor control rates with less toxicity compared to conventional methods.

In the context of systemic therapy, platinum-based radiochemotherapy remains the standard treatment, and early evidence suggests that adding Cetuximab to cisplatin-based therapy does not provide additional benefits in primary treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. Pütz, M., Wenz, F.[2021]

Intensity-modulated radiation therapy (IMRT) has improved the efficacy of treating head and neck squamous cell carcinomas (HNSCC) by allowing for precise targeting of tumors while protecting surrounding healthy tissues.

Despite being traditionally considered low risk for causing nausea and vomiting, recent studies suggest that IMRT may actually increase the incidence of radiation-induced nausea and vomiting (RINV), highlighting the need for further research to understand this side effect better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? "A narrative review". Paiar, F., Cristaudo, A., Gonnelli, A., et al.[2021]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

In a study of 200 head and neck cancer patients, reducing the radiation dose to elective nodal sites from 50Gy to 40Gy did not compromise tumor control, as there were no significant differences in survival or recurrence rates between the two groups after two years.

The lower dose (40Gy) was associated with a significant reduction in salivary gland toxicity at 6 and 18 months, suggesting a potential benefit in minimizing side effects for patients undergoing intensity-modulated radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control. Nevens, D., Duprez, F., Daisne, JF., et al.[2022]

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