Radiotherapy for Head and Neck Cancer

Recruiting at 2 trial locations

Overseen By Ryan Hughes, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Recurrent cancer, Prior radiotherapy, Metastatic disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: up to 165 days

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether six radiotherapy treatments per week are more effective than five for treating head and neck cancer after surgery. It targets individuals with specific types of head and neck cancers, such as those in the throat, mouth, or neck, who require additional treatment post-surgery. Participants should have undergone surgery more than six weeks ago but within 112 days. The trial aims to determine if the accelerated radiotherapy schedule improves outcomes compared to the conventional schedule. As an unphased trial, it provides patients the opportunity to contribute to innovative research that could enhance future cancer treatment strategies.

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

Research has shown that six radiotherapy treatments per week, instead of the usual five, can be safe for people with head and neck cancer. In one study, 89% of patients completed their treatment plans, indicating that most handled the treatment well. Another study found that this treatment schedule can extend patients' lives.

While these studies focus on survival and treatment completion, they suggest that more frequent treatments are generally safe and manageable for most people. However, as with any treatment, side effects or risks may occur. It is important to consult a doctor for personalized advice and to understand all possible outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about accelerated radiotherapy for head and neck cancer because it offers a potentially faster treatment option compared to the conventional approach. While standard radiotherapy typically involves five sessions per week, the accelerated version includes six sessions, with one day offering two treatments. This approach aims to deliver the same overall radiation dose in a shorter period, which could enhance the effectiveness of the treatment by reducing the time cancer cells have to recover and potentially improving patient outcomes.

What evidence suggests that accelerated radiotherapy might be an effective treatment for head and neck cancer?

This trial will compare two treatment approaches for head and neck cancer: accelerated radiotherapy and conventional radiotherapy. Research has shown that accelerated radiotherapy, which participants in this trial may receive, involves more frequent sessions and can better control the cancer at its origin, reducing the likelihood of recurrence. Some evidence also suggests that this method might extend patients' lives. Accelerated radiotherapy could be particularly beneficial for those whose cancer is related to alcohol and tobacco use. ^{1 3 6 7 8}

Who Is on the Research Team?

Ryan Hughes, M.D.

Principal Investigator

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with certain head and neck cancers who've had surgery over 6 weeks ago. It's not specified who can't join, but typically those with poor health or other serious conditions might be excluded.

Inclusion Criteria

I had surgery to remove all visible head and neck cancer.

I am fully active or can carry out light work.

Ability to understand and sign an IRB-approved informed consent document directly, in English or Spanish, and complete study-related forms and activities

Exclusion Criteria

My doctor says I can't have radiation therapy.

I have no active cancer other than in my head or neck.

My head or neck cancer has returned after radiation or surgery followed by radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either accelerated or conventional fractionation radiotherapy

up to 165 days

Daily treatments, Monday-Friday

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Regular follow-up visits at 3, 6, 12, and 24 months post RT

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Radiotherapy
• Conventional Radiotherapy

Trial Overview The study compares two types of radiotherapy: accelerated (6 treatments/week) versus conventional (5 treatments/week), to see which is more effective for head and neck cancer post-surgery.

How Is the Trial Designed?

Group I: Accelerated fractionation (6 Fractions) Experimental Treatment 1 Intervention

6 fractions per week, daily treatment plus twice daily treatment for 1 day Monday-Friday; dosage at the discretion of the treating radiation oncologist per standard of care

Group II: Conventional fractionation (5 Fractions) Active Control 1 Intervention

5 fractions per week, daily treatment Monday-Friday; dosage at the discretion of the treating radiation oncologist per standard of care

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

In a study of 30 patients with locally advanced head and neck cancer, a treatment regimen of accelerated radiation therapy combined with chemotherapy resulted in a high incidence of acute mucositis, increasing from 33.3% in the first week to 93.3% by the end of the fifth week, but showed a decrease to 70% in the sixth week.

The treatment approach demonstrated a significant reduction in complications during the final weeks of therapy, suggesting that the combination of accelerated radiation and chemotherapy with celecoxib may improve tolerance and manage side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant boost chemoradiotherapy in locally advanced head and neck cancer: treatment tolerance and acute side effects. Majdaeen, M., Kazemian, A., Babaei, M., et al.[2015]

In a phase 3 trial involving 840 patients with locally advanced head and neck cancer, conventional chemoradiotherapy showed the best progression-free survival (PFS) rates compared to accelerated radiotherapy-chemotherapy and very accelerated radiotherapy, indicating its superior efficacy.

Very accelerated radiotherapy was associated with higher rates of severe acute mucosal toxicity, suggesting that while it may be faster, it can lead to more serious side effects compared to conventional treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Bourhis, J., Sire, C., Graff, P., et al.[2022]

Hyperfractionated radiation therapy has been shown to improve tumor control in head and neck squamous cell carcinomas, as demonstrated in the EORTC 22791 trial.

Accelerated radiation therapy allows for higher total doses to be delivered in a shorter time, which may be crucial for overcoming rapid tumor cell repopulation during treatment, as supported by recent randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of accelerated fractionation radiotherapy in head and neck squamous cell carcinomas. Bourhis, J., Wibault, P., Lusinchi, A., et al.[2019]

A very accelerated radiotherapy regimen (62 Gy in three weeks) was administered to 46 patients with advanced head and neck cancers, resulting in a 2-year survival rate of 49.4% and a loco-regional control rate of 67%, which are better outcomes compared to conventional radiotherapy.

While nearly all patients experienced severe mucositis (grade 3 or 4), the side effects were manageable, and follow-up suggests that late reactions may not differ significantly from those seen with standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Accelerated radiotherapy: initial results in a series of locally very advanced carcinomas of the upper respiratory and digestive tracts]. Dupuis, O., Bourhis, J., Attal, P., et al.[2007]

Accelerated chemoradiotherapy with concurrent cisplatin or cetuximab in 43 patients with advanced head-and-neck squamous cell carcinoma resulted in a high complete response rate of 74.4% and good locoregional control rates of 82% at 1, 2, and 5 years.

While the treatment was effective, it did have some side effects, with 30.2% of patients experiencing grade 3 mucositis and 27.9% experiencing grade 2 xerostomia, but overall, the toxicities were considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMRT with simultaneous integrated boost and concurrent chemotherapy for locoregionally advanced squamous cell carcinoma of the head and neck. Montejo, ME., Shrieve, DC., Bentz, BG., et al.[2019]

The HARDWINS treatment for advanced head and neck cancer, involving radiation dose escalation up to 64Gy, was delivered safely without any grade 4 acute toxicity, although significant grade 3 toxicity was observed, particularly affecting the pharynx and esophagus.

With a 5-year overall survival rate of 65% and a relapse-free rate of 63%, HARDWINS shows promising outcomes as an alternative to chemoradiation, despite a notable incidence of feeding tube dependence in patients receiving the highest radiation dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer. Waldron, J., Warde, P., Irish, J., et al.[2018]

In a study involving 74 patients with Stage III to IV head and neck cancers, a 5-week accelerated radiotherapy schedule showed a 5-year locoregional control rate of 56% and an overall survival rate of 32%, indicating its potential effectiveness.

While the treatment resulted in significant side effects, including severe mucositis in 77% of patients, the rate of late complications was relatively low at 10.5%, suggesting that this accelerated regimen is feasible and may be a viable option for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An original accelerated radiotherapy schedule in stage III to IV head and neck cancers. Results in a multicenter setting. Allal, AS., Monney, M., Rosset, A., et al.[2019]

The study found that tumors in the head and neck region do not show significant differences in their proliferative capacity based on their site of origin, suggesting that treatment strategies may not need to vary by tumor location.

Aneuploid tumors, which have an abnormal number of chromosomes, exhibited a higher proliferative capacity compared to diploid tumors, indicating they may benefit more from accelerated radiotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proliferative capacity in head and neck cancer. Struikmans, H., Kal, HB., Hordijk, GJ., et al.[2019]

The biphasic accelerated radiotherapy regimen for postoperative treatment of advanced head and neck cancers was feasible, with 93% of the 29 enrolled patients completing the treatment without interruptions.

While most patients experienced mucositis, the acute toxicity was considered acceptable, with no severe Grade 5 reactions, indicating that this treatment approach could be safely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative radiotherapy for head and neck squamous cell carcinomas: feasibility of a biphasic accelerated treatment schedule. Sanguineti, G., Corvo', R., Vitale, V., et al.[2019]

In a study of 51 patients with locally advanced head and neck cancers, the combination of concomitant boost radiotherapy and chemotherapy showed a complete response rate of 51% and an overall response rate of 75.5%, indicating its efficacy in this patient population.

Despite the treatment's effectiveness, only 55% of patients completed it as planned, with the most common side effect being grade 3 mucositis in 49% of patients, highlighting the need for careful patient selection and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated radiotherapy in locally advanced head-neck carcinomas: are concomitant boost and chemotherapy feasible in the routine outpatient-based radiotherapy clinic? Akman, F., Sen, M., Erdag, T., et al.[2007]

Accelerated concomitant boost radiotherapy (RT) is feasible for elderly patients (aged 70 and above) with head and neck carcinoma, showing similar treatment completion rates and toxicities compared to younger patients.

Both elderly and younger patients experienced comparable oncologic outcomes, with similar rates of acute reactions and overall survival, suggesting that age alone should not deter the use of aggressive RT in fit older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and early results of accelerated radiotherapy for head and neck carcinoma in the elderly. Allal, AS., Maire, D., Becker, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8407183/

Hyperfractionated or accelerated radiotherapy for head and ... The results of this meta‐analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814097000790

Accelerated fractionation (AF) compared to conventional ... Conclusions: This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas. A less toxic scheme ...

3. healio.com healio.com/news/hematology-oncology/20231003/accelerated-radiotherapy-effective-in-alcohol-tobaccorelated-head-and-neck-cancer

Accelerated radiotherapy effective in alcohol-, tobacco ... Accelerated radiation treatment could reduce head and neck cancer patient burden in low- and middle-income countries (press release). Available ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1422211/full

Understanding the impact of radiotherapy fractionation on ... This dataset is very useful for investigating the effects of different radiotherapy fractionation schemes on HNSCC patient survival.

5. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/download/24688/29030

A prospective, multicenter DAHANCA study of ... Background: The study aimed to evaluate Hyperfractionated, Accelerated Radiotherapy (HART) with nimorazole for patients with head and neck squamous cell ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-24-02194

The UPGRADE-RT Multicenter Randomized Controlled Trial The primary outcome was normalcy of diet score at 1 year. The secondary outcome was recurrence in electively irradiated nodes at 2 years in the ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814097019440

A randomised trial of accelerated versus conventional ... Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis · Five compared with six fractions per week of conventional radiotherapy ...

8. ar.iiarjournals.org ar.iiarjournals.org/content/36/3/933

A Safe and Effective Option for Head and Neck Cancer in ... Disease-free and overall survival rates were calculated using Kaplan–Meier analysis. Results: Fifty-eight out of 65 patients (89%) completed both courses of ...