Back to resultsHEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers
Primary Purpose
Head and Neck Carcinoma, Head and Neck Carcinoma of Unknown Primary, Hypopharyngeal Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Intensity-Modulated Proton Therapy
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Carcinoma
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic Hospital in ArizonaRecruiting
- Mayo Clinic in ArizonaRecruiting
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A (IMPT, cisplatin)
Arm B (IMPT, cisplatin)
Arm Description
Patients who already underwent surgical resection undergo IMPT for 18 sessions (Monday-Friday) over 24 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 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Incidence of secondary acute effects attributable to radiation therapy
Quality of life (QOL) and financial burden
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.
Quality of life (QOL) and financial burden
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.
Quality of life (QOL) and financial burden
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05075980
Brief Title
HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers
Official Title
HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2022 (Actual)
Primary Completion Date
November 15, 2025 (Anticipated)
Study Completion Date
November 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Carcinoma, Head and Neck Carcinoma of Unknown Primary, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Metastatic Malignant Neoplasm in the Lymph Nodes, Nasal Cavity Carcinoma, Oral Cavity Carcinoma, Oropharyngeal Carcinoma, Paranasal Sinus Carcinoma, Salivary Gland Carcinoma, Skin Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
117 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A (IMPT, cisplatin)
Arm Type
Experimental
Arm Description
Patients who already underwent surgical resection undergo IMPT for 18 sessions (Monday-Friday) over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care.
Arm Title
Arm B (IMPT, cisplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Intensity-Modulated Proton Therapy
Other Intervention Name(s)
IMPT
Intervention Description
Undergo IMPT
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Rate of local/regional control (LRF)
Description
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.
Time Frame
At 2 years
Secondary Outcome Measure Information:
Title
Incidence of acute adverse events
Description
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.
Time Frame
Up to 3 months after radiation therapy
Title
Incidence of late adverse events
Description
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.
Time Frame
Up to 3 years after completion of radiation therapy
Title
Incidence of secondary acute effects attributable to radiation therapy
Time Frame
Up to 3 months after completion of radiation therapy
Title
Quality of life (QOL) and financial burden
Description
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.
Time Frame
Up to 10 years
Title
Quality of life (QOL) and financial burden
Description
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.
Time Frame
Up to 10 years
Title
Quality of life (QOL) and financial burden
Description
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.
Time Frame
Up to 10 years
Title
Regional recurrence rates
Description
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.
Time Frame
Up to 10 years
Title
Local recurrence incidence
Description
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.
Time Frame
Up to 10 years
Title
Distant recurrence rates
Description
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.
Time Frame
Up to 10 years
Title
Invasive disease-free survival (DFS)
Description
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.
Time Frame
From registration until the time of disease recurrence or death due to any cause, assessed up to 10 years
Title
Overall survival (OS)
Description
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.
Time Frame
From registration to death due to any cause, assessed up to 10 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Referral Office
Phone
855-77 6-0015
Email
mayocliniccancerstudies@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott C. Lester, M.D.
Organizational Affiliation
Mayo Clinic in Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Hospital in Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Lisa A. McGee, M.D.
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Lisa A. McGee, M.D.
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Scott C. Lester, M.D.
12. IPD Sharing Statement
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers
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