Hypofractionated Radiation Therapy for Head and Neck Cancer

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: HPV-positive, Prior malignancy, Prior radiation, others

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

Compensation: Varies

Number of Visits: 5

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a phase 1 study to determine the safety of a condensed preoperative radiation regimen (10, 7, or 5 fractions) for the management of head and neck squamous cell carcinoma.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is hypofractionated radiation therapy generally safe for humans?

Studies show that hypofractionated radiation therapy, which involves giving higher doses of radiation over a shorter period, is generally safe for treating head and neck cancers. Most patients experience low-grade side effects, and serious side effects are rare, especially with lower doses like 4 Gy. ^{1 2 3 4 5}

How is hypofractionated radiation therapy unique for head and neck cancer treatment?

Hypofractionated radiation therapy for head and neck cancer is unique because it delivers higher doses of radiation in fewer sessions, which can be effective for both palliative and curative purposes, especially in advanced stages. This approach can improve the quality of life and survival rates for patients who respond well, distinguishing those who may benefit from further curative treatment. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Hypofractionated Radiation Therapy for Head and Neck Cancer?

Research shows that hypofractionated radiotherapy, which involves giving higher doses of radiation over fewer sessions, can be effective for head and neck cancer. In one study, 54% of patients showed complete tumor response, and 65% experienced improved quality of life, indicating potential benefits of this treatment approach. ^{2 7 10 11 12}

Who Is on the Research Team?

Joseph Zenga, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults with specific types of head and neck cancer (HPV-negative squamous cell carcinoma) that can be surgically removed. They must have a certain level of overall health, not have had prior invasive cancers in the last three years, no previous treatment for their current cancer, and agree to use contraception if they can have children.

Inclusion Criteria

I am 18 or older with a type of head or neck cancer that is not linked to HPV and can be removed by surgery.

Ability to understand and sign a written informed consent document

I can take care of myself and am up more than 50% of my waking hours.

Exclusion Criteria

I have not been hospitalized for heart issues in the last 3 months.

I have not had any other cancer besides skin cancer in the last 3 years.

My cancer is HPV-positive squamous cell carcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated preoperative radiation therapy with varying dose levels (46 Gy in 10 fractions, 40 Gy in 7 fractions, or 35 Gy in 5 fractions)

1-2 weeks

5-10 visits (in-person)

Surgery

Participants undergo surgery for resection of remaining disease at the primary site and at-risk nodal basins

6-8 weeks after radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of recurrence-free survival and overall survival

Up to one year

What Are the Treatments Tested in This Trial?

Interventions

• 35 Gy Radiation Therapy
• 40 Gy Radiation Therapy
• 46 Gy Radiation Therapy

Trial Overview The trial is testing different doses of preoperative radiation therapy (46 Gy, 40 Gy, or 35 Gy given in fewer treatments) to see which is safest for treating head and neck squamous cell carcinoma before surgery.

How Is the Trial Designed?

Group I: 46 Gray (Gy) Experimental Treatment 1 Intervention

46 gy of radiation therapy will be administered in 10 fractions.

Group II: 40 Gray (Gy) Experimental Treatment 1 Intervention

40 gy of radiation therapy will be administered in 7 fractions.

Group III: 35 Gray (Gy) Experimental Treatment 1 Intervention

35 gy of radiation therapy will be administered in 5 fractions.

35 Gy 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:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Head and neck cancers

Approved in United States as Radiation Therapy for:

• Breast cancer
• Prostate cancer
• Head and neck cancers
• Pancreatic cancer
• Brain tumors
• Spine tumors
• Liver tumors
• Kidney tumors

Approved in Canada as Radiation Therapy for:

• Breast cancer
• Prostate cancer
• Head and neck cancers
• Pancreatic cancer
• Brain tumors
• Spine tumors
• Liver tumors
• Kidney tumors

Approved in Japan as Radiation Therapy for:

• Breast cancer
• Prostate cancer
• Head and neck cancers
• Pancreatic cancer
• Brain tumors
• Spine tumors
• Liver tumors
• Kidney tumors

Approved in China as Radiation Therapy for:

• Breast cancer
• Prostate cancer
• Head and neck cancers
• Pancreatic cancer
• Brain tumors
• Spine tumors
• Liver tumors
• Kidney tumors

Approved in Switzerland as Radiation Therapy for:

• Breast cancer
• Prostate cancer
• Head and neck cancers
• Pancreatic cancer
• Brain tumors
• Spine tumors
• Liver tumors
• Kidney tumors

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In a study of 81 patients with head and neck cancer treated with high-dose hypofractionated radiotherapy, 63% experienced significant palliative effects lasting a median of 4.6 months, indicating the treatment's efficacy.

Intensity-modulated radiotherapy (IMRT) was associated with lower rates of severe mucositis compared to 2D/3D techniques (26% vs 44%), suggesting that IMRT is the preferred method due to its better safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and toxicity of hypofractionated high-dose intensity-modulated radiotherapy versus 2- and 3-dimensional radiotherapy in incurable head and neck cancer. van Beek, KM., Kaanders, JH., Janssens, GO., et al.[2022]

A fast-track nutritional intervention for head and neck cancer patients undergoing radiotherapy led to significantly better nutritional status, with a lower prevalence of malnutrition (31.9% in the early group vs 69.5% in the conventional group).

Patients in the early intervention group required less nutritional support and experienced fewer emergency visits and hospitalizations three months after treatment, indicating improved overall health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early versus conventional nutritional intervention in head and neck cancer patients before radiotherapy: benefits of a fast-track circuit. González-Rodríguez, M., Villar-Taibo, R., Fernández-Pombo, A., et al.[2021]

In a study of 26 patients with stage IV head and neck cancers, a hypofractionated radiotherapy regimen resulted in a 54% complete response rate and a 23% partial response rate, indicating significant tumor regression.

The split-course radiotherapy technique allowed 61% of patients to qualify for further radical treatment, and 65% reported improved quality of life, highlighting its potential to identify patients who may benefit from curative intent therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Split-Course Radiotherapy in Stage IV Head & Neck Cancer. Biswal, BM., Ruzman, N., Ahmad, NM., et al.[2022]

In a study of 204 head and neck cancer survivors, those who received hypofractionated radiotherapy reported similar or better quality of life compared to those who underwent conventional radiotherapy, despite both groups experiencing significant treatment-related symptoms.

The type of surgical procedure significantly impacted patients' emotional function, highlighting the importance of considering surgical approaches and coordinated therapies to improve quality of life in future head and neck cancer trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life in patients treated for head and neck cancer: a follow-up study 7 to 11 years after radiotherapy. Bjordal, K., Kaasa, S., Mastekaasa, A.[2022]

Out of 324 head and neck squamous cell carcinoma patients undergoing radical radiotherapy, 76 (about 23.5%) discontinued treatment without medical authorization, indicating a significant issue with treatment compliance.

Factors contributing to non-compliance included financial difficulties (24.1%), preference for traditional healers (22.2%), and logistical challenges, particularly among patients living more than 100 km from the treatment center, highlighting the need for targeted support for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India. Pandey, KC., Revannasiddaiah, S., Pant, NK.[2020]

In a phase 1 study involving 12 patients with resected head and neck squamous cell carcinoma, moderately hypofractionated radiation therapy (RT) was found to be well tolerated, with no dose-limiting toxicities reported.

The study determined that a dose of 44.4 Gy in 12 fractions was the maximum tolerated, but 46.5 Gy in 15 fractions was recommended for further testing due to better tolerability and equivalent effectiveness, indicating a promising approach to reduce treatment time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HYPORT: Phase 1 Study of 3-Week Hypofractionated Postoperative Radiation Therapy for Head and Neck Squamous Cell Carcinoma. Moon, DH., Avkshtol, V., Vo, D., et al.[2023]

A genome-wide association study involving 1279 head and neck cancer patients identified significant single nucleotide polymorphisms (SNPs) associated with acute radiation-induced xerostomia, particularly highlighting the SNP rs35542 on chromosome 5q21.3.

The identified SNPs are linked to genes involved in DNA damage response, suggesting that understanding these genetic factors could lead to personalized radiotherapy approaches, potentially reducing toxicities for sensitive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer. Naderi, E., Crijns, APG., Steenbakkers, RJHM., et al.[2021]

In a study of 60 patients with stage I and II squamous cell carcinoma of the oropharynx, accelerated radiotherapy (RT) showed better locoregional control, with 76% of patients achieving a complete response compared to 64% in the conventional RT group after one year.

While the accelerated RT group experienced higher rates of acute toxicities (Grade 2 and 3), the late toxicities were similar between both treatment arms, suggesting that accelerated RT is a viable option despite the increased short-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of conventional fractionation (five fractions per week) and altered fractionation (six fractions per week) in stage I and II squamous cell carcinoma of oropharynx: An institutional study. Poddar, J., Sharma, AD., Kunikullaya, SU., et al.[2019]

In a study of 266 patients with head and neck indolent non-Hodgkin lymphomas, very low-dose radiation (4 Gy) resulted in significantly lower early and late toxicities compared to standard doses (24-30 Gy), making it a safer option for treatment.

The 4 Gy treatment showed minimal short- and long-term toxicity, with no high-grade toxicities reported, suggesting that concerns about radiation-related side effects should not prevent oncologists from considering this effective and potentially curative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low grade, indolent lymphomas of the head and neck: Comparative toxicity of standard versus very low dose radiation therapy. Chelius, M., Chau, K., Yang, J., et al.[2023]

The hypofractionated palliative radiotherapy regimen '0-7-21' (24 Gy in three fractions) demonstrated significant effectiveness in treating head and neck cancers, with 40% of patients achieving complete symptom relief and 31% showing complete tumor size response.

This study, involving 110 patients, found that the 0-7-21 regimen is well-tolerated with an acceptable toxicity profile, providing excellent symptom control and local tumor management, while also requiring less treatment time compared to traditional palliative radiotherapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers. Nguyen, NT., Doerwald-Munoz, L., Zhang, H., et al.[2022]

High-dose, hypofractionated radiotherapy (HFRT) demonstrated a high overall response rate of 79% and a one-year local-progression free rate of 50% in treating head-and-neck malignancies, based on a retrospective analysis of 48 patients.

The study found that delivering doses of 6Gray or higher per fraction improved locoregional control, and increased toxicity was not observed with doses of 8Gray or more, suggesting that HFRT can be both effective and safe for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. Teckie, S., Lok, BH., Rao, S., et al.[2022]

A retrospective analysis of 75 elderly or unfit patients with head and neck cancer showed that a split course hypofractionated radiotherapy (SCH-RT) regimen is effective, achieving local control rates of 72.8% at 12 months and 51.7% at 24 months.

The SCH-RT protocol was well-tolerated, with only 8% of patients experiencing acute grade 3 or higher toxicities, suggesting it could be a viable alternative to palliative care for patients who cannot undergo standard radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Split-course hypofractionated radiotherapy for aged and frail patients with head and neck cancers. A retrospective study of 75 cases. Benhmida, S., Sun, R., Gherga, E., et al.[2020]

Citations

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

Effectiveness and toxicity of hypofractionated high-dose intensity-modulated radiotherapy versus 2- and 3-dimensional radiotherapy in incurable head and neck cancer. [2022]

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

Early versus conventional nutritional intervention in head and neck cancer patients before radiotherapy: benefits of a fast-track circuit. [2021]

3. Malaysia pubmed.ncbi.nlm.nih.gov

Split-Course Radiotherapy in Stage IV Head & Neck Cancer. [2022]

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

Quality of life in patients treated for head and neck cancer: a follow-up study 7 to 11 years after radiotherapy. [2022]

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

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India. [2020]

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

HYPORT: Phase 1 Study of 3-Week Hypofractionated Postoperative Radiation Therapy for Head and Neck Squamous Cell Carcinoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer. [2021]

8. India pubmed.ncbi.nlm.nih.gov

Comparison of conventional fractionation (five fractions per week) and altered fractionation (six fractions per week) in stage I and II squamous cell carcinoma of oropharynx: An institutional study. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Low grade, indolent lymphomas of the head and neck: Comparative toxicity of standard versus very low dose radiation therapy. [2023]

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

0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers. [2022]

11. England pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. [2022]

12. France pubmed.ncbi.nlm.nih.gov

Split-course hypofractionated radiotherapy for aged and frail patients with head and neck cancers. A retrospective study of 75 cases. [2020]