Multimodality Therapy for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Prohibited medications

Disqualifiers: Metastatic disease, Active infection, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating head and neck cancer, specifically squamous cell carcinoma. The study aims to determine if combining chemotherapy, surgery, and radiation can reduce side effects and improve treatment outcomes. After surgery, participants will be assigned to different groups based on their risk level and will receive tailored treatment plans. Individuals with untreated squamous cell carcinoma in the mouth, throat, or voice box, who have not recently undergone major surgery, might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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, it mentions that you cannot use certain prohibited medications during treatment with lapatinib, so it's best to discuss your current medications with the study team.

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

Research has shown that cisplatin, a chemotherapy drug used in the trial, is generally safe for patients with head and neck cancers. Studies indicate that both weekly and every-three-week schedules of cisplatin have similar safety levels, causing side effects at similar rates. However, missing doses can lead to worse outcomes, so adherence to the treatment plan is crucial.

For ipsilateral radiation, research suggests it is safe and effective for certain head and neck cancers, usually causing fewer side effects compared to radiation targeting both sides of the neck.

Bilateral radiation carries some risks, such as skin problems and other long-term side effects. Despite this, it remains a common treatment for head and neck cancers, and many patients manage well with proper care.

Transoral surgery has been shown to be a safe option for treating head and neck cancers. Studies find that most patients do not experience major complications, and it can be safely performed on both younger and older patients.

Overall, the treatments used in this trial have been studied and are generally well-tolerated. However, like any treatment, they come with potential risks. Discussing these with a medical professional is important before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this multimodality therapy for head and neck cancer because it offers a tailored approach based on patients' risk levels. Unlike standard treatments that often involve a one-size-fits-all regimen, this approach customizes therapy intensity: low-risk patients avoid unnecessary treatments after surgery, while medium- and high-risk patients receive targeted radiation and chemotherapy. This stratified approach minimizes exposure to intense treatments for those who might not need them, potentially reducing side effects and improving quality of life. Additionally, the integration of transoral surgery aims to be less invasive, offering quicker recovery times compared to traditional surgical methods.

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

In this trial, all participants will undergo induction chemotherapy and transoral surgery. Research has shown that combining cisplatin with radiation effectively treats head and neck cancer. Studies have found that administering cisplatin weekly or every three weeks results in similar survival rates for these patients. Participants in the medium risk category will receive ipsilateral radiation, targeting one side of the neck, along with weekly cisplatin, as it is considered less harmful. Those in the high risk category will receive cisplatin every three weeks with concurrent bilateral radiation, which treats both sides of the neck and has been linked to better outcomes when combined with other treatments. Transoral surgery, a less invasive procedure, has demonstrated good results for patients with small, clearly defined tumors, helping them live longer while preserving essential abilities like swallowing and speaking. ^{2 6 7 8 9}

Who Is on the Research Team?

Jared Weiss, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

Adults over 18 with previously untreated squamous cell carcinoma in the oral cavity, oropharynx, or larynx that can be removed by transoral surgery. Participants must have good liver and kidney function, acceptable blood counts, normal heart function, and agree to use contraception. Excluded are those with metastatic disease, recent major surgery recovery issues, serious infections or conditions that could risk safety or trial goals.

Inclusion Criteria

My heart's pumping ability is within the normal range.

I agree to use birth control during the study.

My blood tests show I have enough white blood cells, hemoglobin, and platelets.

Exclusion Criteria

My cancer has spread to other parts of my body.

I am not a candidate for the chemotherapy drugs in the initial treatment plan.

My cancer is in an early stage and has not spread to lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Neoadjuvant induction with weekly carboplatin and paclitaxel in combination with daily lapatinib for 6 weeks

6 weeks

Surgery

Transoral surgery for squamous cell carcinoma of the head and neck

1 week

Post-operative Treatment

Risk-adapted treatment: no further treatment, ipsilateral radiation with weekly chemotherapy, or cisplatin with bilateral radiation based on risk category

11 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Bilateral Radiation
• Cisplatin
• Ipsilateral Radiation
• Lapatinib
• Paclitaxel
• Transoral Surgery

Trial Overview

The study tests a combination of treatments for head and neck cancer: starting with chemotherapy drugs (Cisplatin/Carboplatin/Paclitaxel), followed by minimally invasive mouth/throat surgery and radiation therapy (Ipsilateral/Bilateral Radiation). Some may receive Lapatinib. The goal is to reduce side effects while improving treatment outcomes.

How Is the Trial Designed?

Group I: Non-Randomized Single-Arm Experimental Treatment 7 Interventions

All participants will receive induction chemotherapy and transoral surgery. Following surgery, participants will be stratified into a risk category (low, medium, or high). Subjects in the low risk category will receive no further treatment after their transoral surgery. Subjects in the medium risk category will receive ipsilateral radiation concurrent with weekly cisplatin, and subjects in the high risk category will receive cisplatin every three weeks with concurrent bilateral radiation.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase II trial involving 32 patients with advanced head and neck cancer, the aggressive combination of cisplatinum and paclitaxel with hyperfractionated-accelerated radiotherapy resulted in a 5-year overall survival rate of 48% and a disease-free survival rate of 43%.

While the treatment showed promising response rates, with 69% achieving a complete response, it was associated with significant acute toxicities, including high rates of grade 3 mucositis (71%) and erythema (28%), indicating the need for extensive supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. Kuhnt, T., Becker, A., Bloching, M., et al.[2022]

In a phase II study involving 23 patients with head and neck cancer, the combination of paclitaxel and cisplatin resulted in a partial response rate of 32% among evaluable patients, indicating some efficacy.

Despite the observed responses, the significant toxicity, including high rates of asthenia (56%) and other side effects, suggests that this chemotherapy regimen may not be suitable for palliative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma. A phase II trial. Licitra, L., Capri, G., Fulfaro, F., et al.[2020]

Patients with locally advanced oropharyngeal squamous cell carcinoma who received cisplatin (CDDP) had a significantly better 2-year overall survival rate compared to those treated with cetuximab (CTX), with a hazard ratio of 1.68 indicating higher mortality for CTX users.

Cisplatin also resulted in lower overall treatment costs compared to CTX and carboplatin, despite higher rates of antiemetic use and hospital visits for side effects, suggesting it may be a more cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. Amini, A., Eguchi, M., Jones, BL., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8508236/

An Updated Review on Head and Neck Cancer Treatment ...

In another study, 60-day mortality due to aspiration pneumonia occurred in 1.2% of 592 head and neck cancer patients treated with chemoradiation ...

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sciencedirect.com

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Critical review of patient outcome study in head and neck ...

This review critically evaluates the evolution of data-driven approaches in predicting patient outcomes in head and neck cancer patients treated with radiation ...

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Second Malignancy Risk with RT for HPV+ Head & Neck ...

Analysis Clarifies Risk of Second Malignancies with Radiation Therapy for HPV-Positive Head and Neck Cancers. The 10-year cumulative incidence ...

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141 - randomized trial of unilateral versus bilateral neck ...

By last follow-up, 8 patients had died (5 ipsilateral, 3 bilateral). Mean OS was 55.8 versus 52.9 months (p=0.909), RFS 60.2 versus 43.2 months (p=0.244), and ...

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The combination of immunotherapy and radiotherapy demonstrates improved clinical outcomes in R/M HNSCC.

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pmc.ncbi.nlm.nih.gov

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Head and neck cancers: Monitoring quality and reporting ...

The 5‐year overall survival was 69.4% (CI; 64–73.2%). The cumulative incidence of locoregional relapse for the overall study cohort was 18% (CI; ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2667193X25002285

Risk factors and survival impact of severe radiation-related ...

RLTs are common and associated with worse survival among HNC survivors. Identification of modifiable risk factors provides opportunities for prevention.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7533405/

Late side effects of radiation treatment for head and neck cancer

Radiation can increase the risk for skin cancers (basal cell and squamous cell carcinoma) [4]. Regular follow-up by a dermatologist is important. Lymphedema.

9.

redjournal.org

redjournal.org/article/S0360-3016(21)00656-8/fulltext

Patient-Reported Toxicity and Quality-of-Life Profiles in ...

We aimed to characterize the severity and time pattern of patient-reported symptoms and quality of life in a large cohort of patients with HNC treated with ...