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

(VOCAL Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two types of radiotherapy for early glottic cancer, which affects the vocal cords. It compares whether targeting only the vocal cords (Vocal-cord Radiotherapy) is as effective as treating the whole larynx (Complete Larynx Radiotherapy) in controlling the cancer. Researchers aim to assess how each treatment impacts survival, voice quality, swallowing, and overall quality of life. People with early-stage vocal cord cancer who can't or don't want laser surgery might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that vocal-cord only radiotherapy (VC-RT) is a safe treatment for early-stage glottic cancer. Studies have found that patients generally tolerate this treatment well, and modern methods like image-guided radiotherapy enhance its safety. These studies report no major side effects, indicating that the treatment is safe for most patients.

In contrast, complete larynx radiotherapy (CL-RT) has been a common treatment for some time. Although effective, it can cause more side effects than VC-RT. This occurs because it treats a larger area of the throat, potentially affecting voice quality and causing other issues.

Overall, both treatments are considered safe, but VC-RT may have fewer side effects, making it an appealing option for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for early glottic cancer because they offer targeted approaches that could potentially reduce side effects and improve voice quality. Unlike the standard of care, which often involves complete larynx radiotherapy, vocal-cord radiotherapy focuses just on the vocal cords, potentially sparing surrounding healthy tissue. This more precise targeting could lead to fewer complications and a quicker recovery, making it a promising option for patients.

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

This trial will compare Vocal-cord Radiotherapy (VC-RT) with Complete Larynx Radiotherapy (CL-RT) for early-stage glottic cancer. A previous study showed that VC-RT preserved the larynx in 83.1% of patients over five years and achieved an overall survival rate of 92.6%. Additional research indicates that VC-RT effectively controls cancer and maintains good survival rates, with more than 90% of patients surviving five years. These studies suggest that targeting the vocal cords with radiation is safe and effective. Meanwhile, the more traditional approach, CL-RT, has a strong track record for treating early-stage glottic cancer. However, VC-RT is emerging as a potentially equally effective treatment with fewer side effects on voice and swallowing. Both treatments in this trial offer hope for managing this type of cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Houda Bahig

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

David Palma

Principal Investigator

London Health Sciences Centre

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6294272/

Outcomes of Early-stage Glottic Carcinoma Treated with ...

Radiation therapy for EGC in our patients showed reasonable five-year LCR with larynx preservation at 83.1%, DFS 80.0%, five-year OS rate 92.6%, and DSFS rate ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11853244/

Outcome of T2 Glottic Cancer Treated with Radiotherapy ...

Current evidence suggests that radiotherapy (RT) provides excellent locoregional control and survival rates, exceeding 90% at five years for ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0167814025052302

Risk of dysfunctional larynx after radiotherapy for early- ...

The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer.

4.

link.springer.com

link.springer.com/article/10.1007/s00405-023-07904-2

Oncological outcome of vocal cord-only radiotherapy for ...

Vocal cord-only hypofractionated radiotherapy appears to be oncologically safe in early-stage glottic cancer.

5.

waocp.com

waocp.com/journal/index.php/apjcc/article/view/982

Treatment Outcome of Early-stage Laryngeal Carcinoma ...

Conclusion: In early-stage laryngeal carcinomas, radical RT is a function sparing and effective treatment modality with excellent survival rates ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10220095/

Oncological outcome of vocal cord-only radiotherapy for ...

Conclusion. Vocal cord-only hypofractionated radiotherapy appears to be oncologically safe in early-stage glottic cancer. Modern, image-guided ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03759431

Vocal-cord vs. Complete Laryngeal Radiotherapy for Early ...

A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

8.

mdpi.com

mdpi.com/2072-6694/17/4/712

Outcome of T2 Glottic Cancer Treated with Radiotherapy ...

CCRT improves local control, recurrence-free survival, and overall survival in T2N0M0 glottic cancer, albeit with high toxicity.

9.

bmccancer.biomedcentral.com

bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08195-8

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL)

This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this ...