Hypofractionated vs Conventional Radiotherapy for Laryngeal Cancer

(G-FORCE Trial)

Overseen By Sarah Neufeld

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Stage III/IV cancer, Arytenoid involvement, Prior chemotherapy, Synchronous primaries, others

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

Compensation: Varies

Number of Visits: 9

Duration: 5-29 fractions over 5-29 weeks

67 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of delivering radiotherapy for laryngeal cancer, which affects the voice box. One group will receive hypofractionated radiotherapy, a newer method using fewer but stronger doses, while the other group will receive the traditional method with more frequent, smaller doses. The researchers aim to determine which method patients tolerate better. Individuals with early-stage laryngeal cancer (stage 0-II) who have not undergone prior chemotherapy or overlapping radiotherapy may be suitable candidates. As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have uncontrolled illnesses that might affect your participation.

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

Studies have shown that both LT-SABR and IMRT treatments are safe for patients with laryngeal cancer. Research indicates that LT-SABR, a precise radiation therapy, is well-tolerated by patients with early-stage glottic larynx cancer, who have reported positive results.

For IMRT, or Intensity-Modulated Radiation Therapy, studies have found it to be a safe option as well. It reduces side effects like dry mouth and skin thickening compared to older methods. Patients have experienced manageable side effects with both treatments.

Overall, research on these treatments suggests they are safe and well-tolerated, making them promising options for those considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for laryngeal cancer because they offer potentially faster and more precise options compared to conventional methods. The highly conformal hypofractionated radiotherapy, known as LT-SABR, delivers a high dose of radiation in just five sessions, which could reduce treatment time and limit exposure to surrounding healthy tissue. Meanwhile, conventional radiotherapy typically requires around 28 to 29 sessions. By exploring these different approaches, researchers hope to find more efficient ways to manage the condition with fewer side effects and more convenience for patients.

What evidence suggests that this trial's treatments could be effective for laryngeal cancer?

This trial will compare two treatment approaches for laryngeal cancer: LT-SABR and conventional radiotherapy. Research has shown that LT-SABR, a precise type of radiation therapy, is safe and effective for treating early-stage glottic larynx cancer. Studies have found that it works well with fewer side effects, making it a promising choice for patients. Recipients of this treatment have reported satisfaction with the results.

Conventional radiotherapy is another well-known method for treating laryngeal cancer. It involves a longer treatment period but has proven effective in controlling the cancer. Both treatments in this trial aim to target the cancer, but LT-SABR is noted for its efficiency and positive patient feedback. ^{6 7 8 9 10}

Who Is on the Research Team?

David Sher, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with early-stage laryngeal cancer who haven't had certain surgeries or treatments. They must be able to perform daily activities (ECOG 0-2) and agree to use contraception if of childbearing potential. Excluded are those with advanced disease, prior radiation in the area, heavy smokers, or uncontrolled illnesses.

Inclusion Criteria

I have a confirmed diagnosis of squamous cell cancer in my vocal cords.

My larynx cancer is in an early stage and hasn't spread according to scans.

I can take care of myself and perform daily activities.

Exclusion Criteria

Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Subjects may not be receiving any other investigational agents.

I have more than one primary cancer in my head or neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either highly conformal hypofractionated radiotherapy or conventional radiotherapy

5-29 fractions over 5-29 weeks

5-29 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• IMRT
• LT-SABR

Trial Overview The study compares two types of radiotherapy: LT-SABR (a precise high-dose technique) versus IMRT (a standard method). It aims to see which one patients tolerate better during treatment for laryngeal cancer.

How Is the Trial Designed?

Group I: Highly conformal hypofractionated radiotherapy Experimental Treatment 1 Intervention

LT-SABR 42.5 Gy in 5 fractions Low-risk: twice/week Moderate-risk: weekly

Group II: Conventional radiotherapy Experimental Treatment 1 Intervention

Conventional Radiotherapy 63 Gy in 28 fractions (T1) 65.25 Gy in 29 fractions (T2)

IMRT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in European Union as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Canada as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Japan as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Hypofractionated radiotherapy for early-stage squamous cell carcinoma of the glottic larynx shows promising local control rates between 85% and 95%, indicating its efficacy as a treatment option.

While acute laryngeal toxicity is higher with moderate hypofractionation compared to conventional treatment, severe toxicity rates remain similar, suggesting a manageable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] Tonneau, M., Matta, R., Lals, S., et al.[2021]

In a study of 100 patients with T1N0M0 squamous cell carcinoma of the larynx treated with hypofractionated radiotherapy, locoregional control rates were high at 92% at 2 years and 88% at 5 years, demonstrating the efficacy of this treatment approach.

The treatment resulted in excellent cause-specific survival rates of 99% at 2 years and 97% at 5 years, while also preserving voice function, making it a viable option compared to longer fractionation schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of T1N0M0 squamous cell carcinoma of the larynx treated with short-course radiotherapy to a total dose of 50 Gy in 16 fractions: the Birmingham experience. Cheah, NL., Lupton, S., Marshall, A., et al.[2022]

A study of 116 patients with squamous cell carcinomas of the larynx and hypopharynx treated with intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) showed a high overall survival rate of 87% at two years and 82% at three years, indicating its efficacy in managing advanced stage disease.

IMRT-SIB was associated with a lower risk of recurrence and reduced acute toxicity, such as mucositis, compared to traditional radiation therapies, making it a safer option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome and toxicity of intensity-modulated radiotherapy with simultaneous integrated boost in patients with pharyngo-laryngeal cancer. Fondevilla Soler, A., López-Guerra, JL., García Fernández, A., et al.[2020]

In a study of 67 patients with locally advanced head and neck cancer, intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) resulted in significantly less toxicity compared to conventional 3D-conformal radiotherapy, particularly in terms of dysphagia, dermatitis, xerostomia, fibrosis, and lymphedema.

After a median follow-up of 31 months, the locoregional control rates were comparable, with 73% for IMRT-SIB and 78% for 3D-RT, indicating that IMRT-SIB is a feasible treatment option that reduces side effects without compromising effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderately Hypofractionated Intensity-modulated Radiotherapy With a Simultaneous Integrated Boost for Locally Advanced Head and Neck Cancer - Do Modern Techniques Fulfil Their Promise? Wichmann, J., Durisin, M., Hermann, RM., et al.[2021]

In a study of 4,319 patients with early stage squamous cell carcinoma of the glottic larynx, intensity-modulated radiotherapy (IMRT) showed similar overall survival rates compared to traditional 3D conformal radiotherapy (3DCRT), indicating that IMRT can be a safe alternative without compromising patient outcomes.

Patients receiving slight hypofractionation (a different radiation dose schedule) had improved survival compared to those on conventional fractionation, suggesting that adjusting treatment schedules may enhance efficacy in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis. Korpics, MC., Turchan, WT., Rooney, MK., et al.[2020]

This phase 1 study of hypofractionated radiation therapy for early-stage glottic larynx squamous cell carcinoma showed promising results with a 5-fraction stereotactic ablative radiation therapy (SABR) regimen, demonstrating good tolerability and excellent long-term voice quality outcomes.

Despite some patients experiencing dose-limiting toxicities, such as laryngeal edema and dysphagia, the overall efficacy was encouraging, with only 5 local recurrences among 29 patients over a median follow-up of 39.2 months, suggesting that this treatment approach is worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Fractional Dose-Escalation Study of Equipotent Stereotactic Radiation Therapy Regimens for Early-Stage Glottic Larynx Cancer. Sher, DJ., Timmerman, RD., Nedzi, L., et al.[2020]

In a study involving 60 patients with advanced squamous cell cancer of the larynx/hypopharynx, dose-escalated intensity-modulated radiotherapy (IMRT) at a higher dose (DL2) resulted in improved 5-year local control rates (75%) and overall survival (67.6%) compared to a lower dose (DL1) which had 68% local control and 61.9% overall survival.

The treatment demonstrated a low incidence of severe toxicities, with only a few cases of benign pharyngeal strictures reported, indicating that the higher dose of IMRT can be safely administered while achieving better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers. Gujral, DM., Miah, AB., Bodla, S., et al.[2022]

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 40 patients with glottic cancer, hypofractionated radiotherapy (3D-HFRT) was found to be as effective as conventional radiotherapy (3D-CRT) in terms of local control of the tumor, with a 100% control rate for hypofractionated treatment compared to 96% for conventional treatment after 3 years.

Both treatment methods resulted in similar levels of voice quality recovery and minimal toxicity, suggesting that hypofractionated radiotherapy is a well-tolerated alternative for early glottic cancer without compromising oncological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer. Di Nicola, L., Gravina, GL., Marampon, F., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39038521/

Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624029729

Stereotactic Ablative Radiotherapy for T1 to T2 Glottic ... Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03548285?term=Laryngeal%20Cancer&country=United%20States&locStr=United%20States&viewType=Table&rank=7

Stereotactic Ablative Radiotherapy for Early-stage Glottic ... A method used to assign participants to an arm of a clinical study. The types of allocation are randomized allocation and nonrandomized. ... A group or subgroup ...

4. redjournal.org redjournal.org/article/S0360-3016(24)02972-9/abstract

Mature Results From the Phase 2 GLoTtic Larynx-SABR Trial Phase 1 data suggest that stereotactic ablative radiotherapy (SABR) is a viable strategy to reduce the irradiated volume and compress treatment time. This ...

5. ctro.science ctro.science/article/S2405-6308(24)00043-0/fulltext

Stereotactic ablative radiotherapy for treating primary head ... SABR is an innovative, effective and promising treatment modality for small targets, especially in near proximity to organs at risk or in a pre-irradiated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7369226/

Clinical Outcomes for Larynx Cancer Patients Treated with ... Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837514002280

Final long-term results of a phase I/II study of dose- ... Five-year follow-up of this phase I/II study has demonstrated that dose-escalated IMRT at DL2 achieves higher local control, larynx preservation and survival ...

8. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-020-01666-5

long-term and mature outcomes of a prospective randomized ... IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT.

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hed.27877

Efficacy and safety of proton therapy versus intensity‐ ... Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT.

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30506131/

Outcome and toxicity of intensity-modulated radiotherapy ... Conclusions: IMRT-SIB is a safe and feasible radiation treatment technique for pharyngo-laryngeal SCC patients with a tolerable acute toxicity profile.