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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if reducing the number of radiation treatments for head and neck cancer remains safe and effective. Participants will receive one of three reduced doses of radiation therapy (32.5 Gy, 39 Gy, or 42 Gy) to identify the safest and most effective dose for treating cancer. The trial targets individuals who have undergone surgery to remove HPV-negative squamous cell carcinoma in the head or neck and have specific risk factors, such as cancer spread to nearby nerves or lymph nodes.

As an unphased trial, this study provides participants the chance to contribute to significant research that could lead to safer, more effective treatment options.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using lower doses of radiation for head and neck cancer is generally safe. For the 32.5 Gy radiation therapy, studies found that 82% of patients did not experience cancer recurrence in the treated area after about 13 months, and no deaths were reported, indicating it is well-tolerated.

For the 39 Gy radiation therapy, results are typically positive, with about 75% of patients experiencing significant benefits. No serious complications have been reported, suggesting it is safe.

Regarding the 42 Gy radiation therapy, other studies have demonstrated that lower doses are safe. While radiation can cause side effects, these studies suggest that the doses used are safe and manageable.

It is important to remember that radiation therapy can have side effects, but these studies support that the treatments being tested are generally safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these reduced-dose radiotherapy treatments for head and neck cancer because they aim to minimize side effects while maintaining effectiveness. Unlike the standard higher-dose radiation therapies, which can cause significant damage to healthy tissues, these lower-dose options (32.5 Gy, 39 Gy, and 42 Gy) are delivered in fewer fractions. This approach could potentially lead to a better quality of life for patients by reducing the severity of side effects and shortening treatment times, while still effectively targeting cancer cells.

What evidence suggests that this trial's radiation treatments could be effective for head and neck cancer?

Research has shown that lower doses of radiation can effectively treat head and neck cancers. In this trial, participants may receive one of three different radiation treatments. The 32.5 Gy radiation option uses a focused radiation treatment called stereotactic body radiotherapy (SBRT), which has shown promising results in controlling cancer with fewer side effects. The trial also tests the 39 Gy and 42 Gy treatments, using modern techniques to control cancer and reduce side effects. Overall, these lower-dose radiation options aim to manage cancer while minimizing treatment-related harm. ^{1 4 6 7 8}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10605184/

The Evolving Role of Stereotactic Body Radiation Therapy ... This review aims to explore SBRT's role in different HNC scenarios. It has the potential to greatly impact the clinical practice.

3. mdpi.com mdpi.com/2072-6694/16/11/2096

Stereotactic Body Radiotherapy as a Curative Treatment ... Stereotactic body radiotherapy as a curative treatment for de novo mucosal carcinoma of the head and neck: a feasible alternative option for fragile patients ...

4. mayo.edu mayo.edu/research/clinical-trials/tests-procedures/radiation-therapy

Radiation Therapy Clinical Trials This trial aims to see whether adding peposertib to radiation therapy is safe and works well in treating patients with head and neck cancer. Study of 177Lu ...

5. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00155-0/fulltext

Oncologic and Functional Outcomes After Stereotactic ... We report oncologic and functional outcomes for patients treated with stereotactic body radiation therapy (SBRT) to high-grade MESCC.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11844808/

Current State of Stereotactic Body Radiation Therapy for ... Although the freedom from biochemical failure rate at 5 years was 100% in the 47.5 Gy and 50 Gy cohorts, the 50 Gy cohort experienced increased high grade late ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850024003539

Highs and Lows of Spatially Fractionated Radiation Therapy The most common SFRT dose was 20 Gy in 1 fraction with 88% of patients receiving follow-up whole tumor radiotherapy to a median EQD2 dose of 32.5 Gy (=10).

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02388932

Stereotactic Body Radiation Therapy in Treating Patients ... This phase I trial studies the side effects and best dose of stereotactic body radiation therapy (SBRT) in treating participants with head and neck cancer ...