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

Trial Summary

What is the purpose of this trial?

The study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.

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.

What data supports the effectiveness of reduced-dose radiotherapy for head and neck cancer?

Research shows that Intensity Modulated Radiation Therapy (IMRT) and Image Guided Radiation Therapy (IGRT) can improve treatment for head and neck cancer by better targeting tumors and preserving healthy tissue, leading to similar tumor control with fewer side effects compared to traditional methods. Intraoperative radiotherapy has also shown promise in controlling head and neck cancer with reasonable side effects, although more studies are needed to compare it with standard treatments. ^{1 2 3 4 5}

Is reduced-dose radiotherapy for head and neck cancer generally safe for humans?

Reduced-dose radiotherapy, particularly using techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT), is generally considered safe and can reduce side effects compared to traditional methods. However, some side effects like nausea and vomiting may still occur, and there are uncertainties about long-term effects such as secondary cancers and swallowing difficulties. ^{4 6 7 8 9}

How is reduced-dose radiotherapy different from other treatments for head and neck cancer?

Reduced-dose radiotherapy, specifically using Intensity-Modulated Radiation Therapy (IMRT), is unique because it allows for precise targeting of the tumor while minimizing damage to surrounding healthy tissues. This approach can maintain effective tumor control while reducing side effects compared to conventional radiation therapy. ^{1 4 9 10 11}

Research Team

Chris McLaughlin, M.D.

Principal Investigator

UVA

Eligibility Criteria

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

My cancer has spread to distant parts of my body.

Participant is a prisoner

Pregnancy or lactation

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Systematic review of intraoperative radiation therapy for head and neck cancer. [2023]

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

Advances in radiotherapy for head and neck cancer. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. [2021]

5. France pubmed.ncbi.nlm.nih.gov

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

6. Italy pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. [2017]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

8. United States 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". [2021]

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

Intensity-modulated radiotherapy for head and neck cancer. [2007]

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

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers. [2022]

11. Ireland 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. [2022]