HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers

Head and Neck Carcinoma Clinical Trial

Official title:

HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05075980
• Other study ID #: GMROR2171
• Secondary ID: NCI-2021-0970621
• Status: Recruiting
• Phase: Phase 2
• Start date: February 16, 2022
• Est. completion date: November 15, 2026

Study information

• Verified date: March 2024
• Source: Mayo Clinic
• Contact: Clinical Trials Referral Office
• Phone: 855-77 6-0015
• Email: mayocliniccancerstudies[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial tests whether intensity modulated proton therapy after surgery works to shrink tumors in patients with head and neck cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors.

Description:

PRIMARY OBJECTIVE:

I. The primary goal is to evaluate the local-regional control among subjects in both arms at 2 years after study registration.

SECONDARY OBJECTIVES:

I. To determine overall survival progression free survival local, regional, distant recurrence risks, and infield and outfield recurrence in the trial at 2 years after study registration.

II. To determine the rate and duration of grade 3+ acute adverse events from treatment start to 30 days after radiation completion date).

III. To determine the incidence of secondary acute effects attributable to radiotherapy (e.g. percutaneous endoscopic gastrostomy [PEG] tube placement, duration and dose of narcotic analgesia required, weight loss, and hospitalization days).

IV. To determine the impact of treatment on patient reported quality of life. V. To objectively quantify the severity of oral mucositis during and following radiotherapy.

EXPLORATORY OBJECTIVES:

I. To estimate direct and indirect costs of the study regimen and compare these with standard of care treatment techniques.

II. To correlate histopathologic, molecular, and tumor genetic/epigenetic alterations with clinical outcomes.

III. To correlate circulating biomarkers (microribonucleic acid [miRNA], circulating tumor deoxyribonucleic acid [ctDNA]) with clinical outcomes.

IV. To determine adverse events and patient reported outcomes related to abbreviated concomitant chemotherapy.

V. To determine incidence and severity of late effects attributable to radiotherapy at 1-3 years after treatment.

VI. To qualitatively evaluate patient beliefs regarding tradeoffs of cancer control, treatment time, cost, acute side effects, and late side effects.

VII. To determine cancer out comes, adverse events, and patient reported outcomes and compare across head and neck subsites, between those aged 65 to those age < 65 at date of enrollment, between male and female, and in the adjuvant population between time to total package completion (< 9 weeks vs weeks, surgery day 0) and by treatment with and without chemotherapy.

VIII. To evaluate the predictive relationship of linear energy transfer (LET) weighted modeling using an relative biologic enhancement (RBE) based model and RBE independent model with grade 3+ acute and late toxicity.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM A: Patients who already underwent surgical resection undergo intensity modulated proton therapy (IMPT) for 18 sessions (Monday-Friday) over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin intravenously (IV) over 1-2 hours per standard of care. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT or PET/MRI during screening and follow-up. Patients may optionally undergo blood sample collection throughout the trial.

ARM B: Patients undergo surgical resection and then IMPT for 15 sessions (Monday-Friday) over 19 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care. Patients undergo CT or MRI and PET/CT or PET/MRI during screening and follow-up. Patients may optionally undergo blood sample collection throughout the trial.

After completion of study treatment, patients are followed up within 21 days, every 3 months for 2 years, and then every 6-12 months for 5-10 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 117
• Est. completion date: November 15, 2026
• Est. primary completion date: November 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years

• Histological confirmation of a newly diagnosed non-human papillomavirus (HPV) associated malignant epithelial cancer in the head and/or neck. Diagnosis requires confirmation of p16 and/or HPV DNA negativity for oropharyngeal and unknown primary sites. p16 positivity in skin cancers is allowed

• Primary lesion located in the nasal cavity, paranasal sinuses, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, lymph nodes (unknown primary or metastasis from head and neck [HN]-skin primary) or skin cancer where lymph node radiation is recommended

• NOTE: Patients with primary lesions in the larynx must have a T3 primary, bulky T2 primary (> 6 cc), and/or at least 1 regional lymph node

• Confirmation of American Joint Committee on Cancer (AJCC) 8th edition defined M0 established by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI)

• Eastern Cooperative Oncology Group (ECOG) performance status (0-1 prior to initial treatment)

• Able to provide written informed consent

• Able to complete questionnaires independently or with assistance

• Willing to return to enrolling institution for follow up during the observation phase

• Hemoglobin >= 8.0 g/dl (within 8 weeks of registration)

• Platelets >= 75,000 cells/mm^3 (within 8 weeks of registration)

• Absolute neutrophil count > 1500 cells/mm^3 (within 8 weeks of registration)

• Coronavirus disease 2019 (Covid-19) testing per institutional standard. If pre-treatment testing, patients should be negative prior to starting treatment or symptom free for at least 14 days from documented positive test. Vaccination status should be documented

Exclusion Criteria:

• Pregnant women (serum pregnancy test required before treatment per department policy)

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy

• NOTE: Patients known to be HIV positive, but without clinical evidence of immunocompromised state, are eligible for this trial

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Other active malignancy =< 2 years prior to registration

• EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix and prostate cancer with a Gleason score of 6 or less

• NOTE: If there is a history or prior malignancy, they must not be receiving ongoing anticancer treatment

• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• Prior radiation therapy that would have a clinically significant overlap with the intended head/neck radiation

• Unable to receive proton therapy because of extensive metallic hardware in close proximity to treatment site, logistical circumstances, or any other reason

• Any of the following diagnoses: HPV-associated squamous cell carcinoma, germ cell tumors, hematologic malignancies, neuroendocrine malignancies, adenoid cystic carcinoma, sarcomas of bone, benign tumors

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Cutaneous Squamous Cell Carcinoma of the Head and Neck
• Head and Neck Carcinoma
• Head and Neck Carcinoma of Unknown Primary
• Head and Neck Neoplasms
• Hypopharyngeal Carcinoma
• Laryngeal Carcinoma
• Metastatic Malignant Neoplasm in the Lymph Nodes
• Nasal Cavity Carcinoma
• Neoplasms
• Oral Cavity Carcinoma
• Oropharyngeal Carcinoma
• Paranasal Sinus Carcinoma
• Salivary Gland Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Cisplatin
Given IV

Procedure:
• Intensity-Modulated Proton Therapy
Undergo IMPT

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Procedure:
• Computed Tomography
Undergo CT or PET/CT
• Magnetic Resonance Imaging
Undergo MRI or PET/MRI
• Positron Emission Tomography
Undergo PET/CT or PET/MRI
• Biospecimen Collection
Undergo blood sample collection

Locations

Country	Name	City	State
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of local/regional control (LRF)	The 2-year LRF rate will be estimated by counting the number of patients with a local or regional failure and dividing by the total number of eligible patients.	At 2 years
Secondary	Incidence of acute adverse events	The maximum grade for each type of acute adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 3 months after radiation therapy
Secondary	Incidence of late adverse events	The maximum grade for each type of late adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 3 years after completion of radiation therapy
Secondary	Incidence of secondary acute effects attributable to radiation therapy	The electronic health record will be reviewed for treatments related to secondary acute effects such as PEG tube placement, duration and dose of narcotic analgesia required, weight loss, and hospitalization days.	Up to 3 months after completion of radiation therapy
Secondary	Quality of life (QOL) and financial burden - MDADI	MD Anderson Dysphagia Inventory (MDADI) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.	Up to 10 years
Secondary	Quality of life (QOL) and financial burden - EQ-5D-5L	European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.	Up to 10 years
Secondary	Quality of life (QOL) and financial burden - OMWQ-HN	Oral Mucositis Weekly Questionnaire (OMWQ-HN) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.	Up to 10 years
Secondary	Regional recurrence rates	The regional head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/distant head and neck cancer recurrence and death.	Up to 10 years
Secondary	Local recurrence incidence	The local head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be regional/distant head and neck cancer recurrence and death.	Up to 10 years
Secondary	Distant recurrence rates	The distant head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/regional head and neck cancer recurrence and death.	Up to 10 years
Secondary	Invasive disease-free survival (DFS)	The DFS will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals.	From registration until the time of disease recurrence or death due to any cause, assessed up to 10 years
Secondary	Overall survival (OS)	The OS will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals.	From registration to death due to any cause, assessed up to 10 years