Reduced-Dose Radiotherapy for Head and Neck Cancer

(HART-HN Trial)

Overseen By Igli Arapi

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Extranodal extension, Positive margin, HPV-positive, others

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

Compensation: Varies

Number of Visits: 7

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new radiation treatment for patients with head and neck cancer after surgery. The goal is to see if this method is as safe and effective as the traditional longer course of treatment.

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

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 reduced-dose radiotherapy safe for humans?

Research shows that reduced-dose radiotherapy, including hypofractionated and stereotactic body radiation therapy (SBRT), has been studied for safety in treating prostate and head-and-neck cancers. While some studies report it as safe, the safety data is still considered controversial and more research is needed to confirm its safety across different conditions. ^{1 2 3 4 5}

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

Reduced-dose radiotherapy for head and neck cancer uses a precise method called stereotactic body radiation therapy (SBRT) to deliver high doses of radiation in fewer sessions, which can be beneficial for patients who cannot undergo traditional long courses of treatment. This approach aims to target the tumor more accurately while minimizing damage to surrounding healthy tissue, making it suitable for elderly or medically unfit patients. ^{1 4 6 7 8}

What data supports the effectiveness of the treatment Reduced-Dose Radiotherapy for Head and Neck Cancer?

Research shows that hypofractionated stereotactic body radiotherapy (SBRT) can be effective for head and neck cancers, with studies indicating good local control rates and acceptable side effects. For instance, a study on high-risk salivary gland malignancies found that SBRT provided good local control and survival rates, suggesting its potential effectiveness in similar head and neck cancer treatments. ^{4 8 9 10 11}

Who Is on the Research Team?

Musaddiq J. Awan

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults with certain types of head and neck cancers that have been surgically removed but carry intermediate risk factors for recurrence. Participants must be in good general health, psychologically able to complete the study, not pregnant or breastfeeding, willing to use contraception if of childbearing potential, and without recent serious heart issues or other invasive malignancies.

Inclusion Criteria

I am a woman who is either postmenopausal, surgically sterile, or willing to use two forms of birth control.

My cancer has one of the specific risk factors like spreading to lymph nodes or deep growth.

I am 18 or older and had surgery to completely remove HPV-negative squamous cell carcinoma in my head or neck.

Exclusion Criteria

I haven't been hospitalized for heart issues in the last 3 months.

I am not pregnant and willing to use contraception during and 6 months after treatment.

I have had radiation therapy to my head or neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated radiation therapy in 5, 8, or 10 fractions depending on the assigned group

1-2 weeks

5-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after radiation therapy

12 months

Regular visits at weeks 2, 4, 6 and months 3, 6, 9, 12

What Are the Treatments Tested in This Trial?

Interventions

• 32.5 Gy Radiation Therapy
• 39 Gy Radiation Therapy
• 42 Gy Radiation Therapy

Trial Overview The trial is testing three different doses of radiation therapy (42 Gy, 39 Gy, and 32.5 Gy) given over fewer treatment sessions than usual to see which is safest for patients with resected head and neck squamous cell carcinoma who are at an intermediate risk of cancer returning.

How Is the Trial Designed?

Group I: 42 Gray (Gy) Radiation Experimental Treatment 1 Intervention

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

Group II: 39 Gray (Gy) Radiation Experimental Treatment 1 Intervention

39 gy of radiation therapy will be administered in 8 fractions.

Group III: 32.5 Gray (Gy) Radiation Experimental Treatment 1 Intervention

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

32.5 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:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

Approved in United States as Radiation Therapy for:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

Approved in Canada as Radiation Therapy for:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

Approved in Japan as Radiation Therapy for:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

Approved in China as Radiation Therapy for:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

Approved in Switzerland as Radiation Therapy for:

• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer
• Gynecologic cancers

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 10 patients with high-risk salivary gland malignancies, the use of hypofractionated stereotactic body radiotherapy (SBRT) after intensity-modulated radiation therapy resulted in an impressive 3-year locoregional control rate of 88%, indicating effective treatment for this challenging condition.

While the treatment was generally well-tolerated, some patients experienced serious late toxicities, such as graft ulceration and osteoradionecrosis, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMRT with Stereotactic Body Radiotherapy Boost for High Risk Malignant Salivary Gland Malignancies: A Case Series. Karam, SD., Rashid, A., Snider, JW., et al.[2021]

Hypofractionated stereotactic body radiation therapy (SBRT) for early-stage glottic laryngeal cancer is safe and feasible, with a significant reduction in treatment duration from 15 to 5 fractions while maintaining acceptable toxicity levels.

After a median follow-up of 13.4 months, the treatment showed an 82% local disease-free survival rate and a 100% overall survival rate, indicating promising efficacy comparable to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial. Schwartz, DL., Sosa, A., Chun, SG., et al.[2018]

In a study of 25 head and neck cancer patients treated with hypofractionated stereotactic radiotherapy (hSRT) using CyberKnife, there was a high response rate of 96%, with 18 patients achieving complete responses and 6 partial responses after a median follow-up of 28 months.

The study found that smaller planning target volumes (PTV ≤ 20 cm³) were associated with significantly better progression-free survival (92%) and overall survival (100%) compared to larger volumes, indicating that both the size of the treatment area and initial response to treatment are important predictors of patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. Yamazaki, H., Ogita, M., Himei, K., et al.[2018]

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]

The study found that using HBO-4 in combination with hypofractionated radiation therapy significantly improved the complete clinical response rate in patients with locally advanced squamous cell carcinoma of the head and neck, with 84% of patients in the HBO-4 group achieving complete responses compared to 52% in the air group.

While acute toxicities were similar between the two treatment arms, there was a trend toward more severe late complications in the HBO-4 group, indicating the need for careful monitoring and further research into optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial. Haffty, BG., Hurley, R., Peters, LJ.[2004]

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 systematic review of studies on stereotactic body radiation therapy (SBRT) for prostate cancer found that most patients experienced mild to moderate side effects, with severe toxicity occurring in less than 3% of cases, indicating that SBRT is generally well tolerated.

The review identified important dosimetric factors that influence toxicity, such as recommended dose constraints for the bladder, urethra, and rectum, which can help optimize treatment safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. Wang, K., Mavroidis, P., Royce, TJ., et al.[2022]

Moderately hypofractionated external beam radiotherapy (2.4-3.4 Gy per fraction) provides similar biochemical control for localized prostate cancer as conventional radiotherapy, without increasing late toxicity, making it a preferred treatment option for many patients.

Ultrahypofractionated radiotherapy (SBRT, at least 5 Gy per fraction) shows promising results in biochemical control and acceptable toxicity, particularly in low- and intermediate-risk prostate cancer, suggesting it could be a viable alternative to traditional treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom? Roy, S., Morgan, SC.[2020]

A review of 26 studies involving men with prostate cancer found that both external beam radiation therapy (EBRT) and brachytherapy (BT) have similar long-term rates of freedom from biochemical failure (FFBF), with 10-year rates ranging from 20-90% depending on risk group.

Overall survival and cancer-specific mortality rates did not significantly differ among various radiation therapy modalities, and serious toxicities were rare (<5%), suggesting that treatment choice can be personalized based on patient risk factors and quality of life considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer. Zaorsky, NG., Shaikh, T., Murphy, CT., 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]

Stereotactic body radiation therapy (SBRT) is a highly precise treatment for head and neck cancer that delivers high doses of radiation directly to tumors while minimizing damage to surrounding healthy tissue, making it suitable for patients who cannot undergo traditional radiation therapy.

Recent studies suggest that combining SBRT with immunotherapy in early treatment stages shows promising results, indicating potential for improved outcomes in head and neck cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand? Mohamad, I., Karam, I., El-Sehemy, A., et al.[2023]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

IMRT with Stereotactic Body Radiotherapy Boost for High Risk Malignant Salivary Gland Malignancies: A Case Series. [2021]

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

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial. [2018]

3. Greece pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. [2018]

4. Malaysia pubmed.ncbi.nlm.nih.gov

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

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

Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial. [2004]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. [2022]

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

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom? [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer. [2022]

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand? [2023]