Vocal-cord vs. Complete Larynx Radiotherapy for Early Glottic Cancer

(VOCAL Trial)

Recruiting at 2 trial locations

Overseen By Diane Trudel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Previous head and neck irradiation, Pregnancy, Prior invasive malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

155 Participants Needed

Trial Summary

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 team or your doctor.

What data supports the effectiveness of the treatment Complete Larynx Radiotherapy for early glottic cancer?

Complete Larynx Radiotherapy (CL-RT) has shown excellent local control rates for early glottic cancer, although it can lead to significant side effects like voice and swallowing issues. A study also found that focused vocal cord radiotherapy (VC-RT) provided similar local control outcomes with improved voice quality compared to CL-RT. ^{1 2 3 4 5}

Is complete larynx radiotherapy safe for humans?

Complete larynx radiotherapy (CL-RT) is generally safe for humans, but it can have significant side effects like voice and swallowing problems, and a higher long-term risk of issues with blood flow to the brain. There is no prospective safety data for vocal-cord only radiotherapy (VC-RT), but retrospective studies suggest it may have fewer side effects. ^{2 3 5 6 7}

How does Vocal-cord Radiotherapy differ from other treatments for early glottic cancer?

Vocal-cord Radiotherapy (VC-RT) focuses radiation only on the vocal cords, potentially improving voice quality and reducing side effects compared to Complete Larynx Radiotherapy (CL-RT), which treats the entire larynx and can lead to more significant voice and swallowing issues. ^{2 3 4 5 8}

What is the purpose of this trial?

This is a multicentrer, randomized Bayesian Phase II trial for patients with early stage (T1N0) glottic squamous cell carcinoma treated with radical radiotherapy. The primary objective is to assess the non-inferiority of local control achieved with vocal-cord only radiotherapy (VC-RT) compared to complete larynx radiotherapy (CL-RT) in T1N0 glottic laryngeal squamous cell cancer, measured at 2-years after treatment. Secondary outcomes include overall survival, as well as voice impairment, dysphagia and quality of life, measured respectively by the voice handicap index -10 (VHI-10), the MD Anderson Dysphagia Inventory (MDADI) and the MD Anderson Symptom Inventory- Head and Neck module (MDASI-HN). Patients will be randomized in a 1:3 ratio to CL-RT (39 patients) and VC-RT (116 patients) arms. There will be stratification by tumor stage (T1a/T1b) and by institution. An interim analysis is planned after the first 55 patients enrolled on the experimental arm have a 6-month follow-up.

Research Team

Houda Bahig

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

David Palma

Principal Investigator

London Health Sciences Centre

Eligibility Criteria

This trial is for people with early-stage glottic cancer (T1N0) who can't have or don't want laser surgery. They should be in decent physical shape and not have had other cancers (except certain skin cancers) in the last 2 years, no prior radiation to the head and neck, and not be pregnant or breastfeeding.

Inclusion Criteria

Ability to provide written informed consent.

I can take care of myself and am up and about more than half of my waking hours.

My vocal cord cancer is in an early stage and I am planning to have radiation therapy.

Exclusion Criteria

I have had radiation therapy on my head or neck.

I don't have any health issues that would stop me from safely receiving or following up after radiotherapy.

I have been cancer-free for at least 2 years, except for non-melanoma skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vocal-cord only radiotherapy or complete larynx radiotherapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 2-month, 6-month, 1-year, and 2-year intervals

Interim Analysis

An interim analysis is conducted after the first 55 patients enrolled on the experimental arm have a 6-month follow-up

6 months

Treatment Details

Interventions

• Complete Larynx Radiotherapy
• Vocal-cord Radiotherapy

Trial Overview The study compares two types of radiotherapy for early vocal cord cancer: one that targets only the vocal cords, and another that treats the entire larynx. It's a randomized trial where patients are put into groups by chance to see which method works best at controlling cancer without affecting voice quality.

Participant Groups

Group I: Vocal-cord Radiotherapy Experimental Treatment 1 Intervention

Group II: Complete Larynx Radiotherapy Active Control 1 Intervention

Complete Larynx Radiotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Radical Radiotherapy for:

• Early-stage glottic squamous cell carcinoma

Approved in United States as Complete Larynx Radiotherapy for:

• T1N0 glottic laryngeal squamous cell cancer

Approved in Canada as Radical Radiotherapy for:

• Stages 1 and 2 carcinoma of the glottis

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

London Health Sciences Centre

Collaborator

Trials

151

Recruited

60,400+

Findings from Research

In a review of 91 early vocal cord carcinomas treated with radiation therapy, the 5-year survival rates were high, with 86% crude survival and 95% determinate survival, indicating effective treatment outcomes.

The study found that primary irradiation alone achieved a 5-year cure rate of 77%, and local recurrences were successfully managed in 12 out of 21 patients through surgical interventions, highlighting the importance of follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of radiation therapy of early carcinoma of the vocal cords. Inoue, T., Shigematsu, Y., Sato, T.[2019]

This Phase II trial will compare the local control (LC) rates of focused vocal cord radiotherapy (VC-RT) to complete larynx radiotherapy (CL-RT) in 155 patients with early glottic squamous cell cancer, aiming to provide the first prospective evidence on the safety and efficacy of VC-RT.

If successful, VC-RT could offer similar local control outcomes with potentially fewer side effects, such as voice impairment and swallowing difficulties, compared to the traditional CL-RT, thus changing the standard treatment approach for early glottic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial. Bahig, H., Rosenthal, DI., Nguyen-Tan, FP., et al.[2023]

In a study of 58 laser cordectomy cases and 40 cases treated with radiotherapy (RT) or chemoradiotherapy (CRT) for early glottic carcinoma, type I and II cordectomies showed no significant difference in voice quality compared to RT for T1 glottic carcinoma, but T1RT had better outcomes than type III cordectomy.

For T2 glottic carcinoma, type IV cordectomy had similar voice quality to RT or CRT, while types V and VI cordectomies resulted in worse voice quality, indicating that the type of cordectomy significantly impacts post-treatment voice outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of voice quality after laser cordectomy with that after radiotherapy or chemoradiotherapy for early glottic carcinoma. Tomifuji, M., Araki, K., Niwa, K., et al.[2013]

Both surgery and radiotherapy are effective for early-stage laryngeal cancer, providing high rates of local control and cure, with similar outcomes for radiation therapy, cordectomy, and hemilaryngectomy.

At our institution, about 80% of patients with untreated T1 and T2 vocal cord cancers are treated with radiation therapy, while transoral laser excision is reserved for select well-defined T1 tumors to preserve voice quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early laryngeal cancer. Hinerman, RW., Mendenhall, WM., Amdur, RJ., et al.[2019]

In a study of 34 patients with early-stage T1a glottic cancer, single vocal cord irradiation (SVCI) achieved a high local control rate of 96.8% at both 3 and 5 years, indicating its efficacy in treating this type of cancer.

SVCI was associated with low levels of acute toxicity, with only 6% of patients experiencing severe radiation dermatitis, and no severe late toxicity events reported, suggesting it is a safe treatment option with reasonable voice recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of single vocal cord irradiation as a treatment strategy for T1a glottic cancer. Chung, SY., Lee, CG.[2021]

A novel 4D conformal technique for single vocal cord irradiation (SVCI) demonstrated a high local control rate of 93% over five years in 164 T1a patients with vocal cord cancer, indicating its efficacy in treating early glottic cancer.

The technique allows for precise irradiation within 1-2mm accuracy, effectively sparing the contralateral vocal cord and surrounding normal tissues, suggesting that hypofractionated SVCI could be a viable alternative to traditional laser surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single vocal cord irradiation: a competitive treatment strategy in early glottic cancer. Levendag, PC., Teguh, DN., Keskin-Cambay, F., et al.[2022]

The VoiceS study is a pioneering phase III trial that will compare single vocal cord irradiation (SVCI) with transoral CO2-laser microsurgical cordectomy (TLM) in 34 patients with early-stage glottic cancer, focusing on voice quality over 24 months.

The primary goal is to assess patient-reported voice quality using the voice handicap index, while also evaluating tumor control and treatment toxicity, which could enhance treatment decisions for early-stage glottic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial. Reinhardt, P., Giger, R., Seifert, E., et al.[2022]

Supracricoid partial laryngectomies (SCPLs) are effective in managing selected recurrences of glottic-supraglottic cancer after radiation therapy, achieving a high disease-free survival rate of 95.5% at both 3 and 5 years.

Despite a complication rate of 27% for early and 17.9% for late postoperative issues, SCPLs allow for excellent functional outcomes, with 97.4% of patients achieving decannulation and satisfactory swallowing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supracricoid partial laryngectomies after radiation failure: a multi-institutional series. Pellini, R., Pichi, B., Ruscito, P., et al.[2022]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

Results of radiation therapy of early carcinoma of the vocal cords. [2019]

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

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of voice quality after laser cordectomy with that after radiotherapy or chemoradiotherapy for early glottic carcinoma. [2013]

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

Early laryngeal cancer. [2019]

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

Feasibility of single vocal cord irradiation as a treatment strategy for T1a glottic cancer. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Single vocal cord irradiation: a competitive treatment strategy in early glottic cancer. [2022]

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

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial. [2022]

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

Supracricoid partial laryngectomies after radiation failure: a multi-institutional series. [2022]