search
Back to results

Study of Mucosal Sparing Adjuvant Radiotherapy After Surgical Exploration in HPV+ Head and Neck Cancer of Unknown Primaries

Primary Purpose

Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Medical Chart Review
Patient Observation
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients meet criteria for intensity-modulated proton therapy (IMPT) treatment for oropharyngeal cancer

    • If IMPT is declined by patient's insurance, they can be treated with standard of care IMRT using the same applicable standard of care procedures outlined in the procedures manual
  • Meet criteria for adjuvant chemotherapy (if applicable)
  • Histological confirmation of human papillomavirus (HPV)+ squamous cell carcinoma as defined by neck node pathology. HPV positivity will be defined as positive staining for p16 and HPV deoxyribonucleic acid (DNA) in situ hybridization (ISH). (If discordant, ribonucleic acid [RNA] ISH will be run for confirmatory testing)

  • Clinical stage T0 N1-N3 and confirmed pathologic stage T0 N1-N2 M0 (American Joint Committee on Cancer [AJCC] 8th edition) with one of the following risk factors:

    • Lymph node >= 3 cm
    • >= 2 positive lymph nodes
    • Presence of extracapsular extension
    • > 1 nodal level involved
  • Absence of distant metastases on standard diagnostic workup, prior to registration (chest computed tomography [CT], chest x-ray [CXR], or positron emission tomography [PET]/CT)
  • Able to undergo pre-operative Q-clear series PET/CT head/neck for diagnostic workup of occult primary and nodal disease

  • Able to undergo transoral surgery and neck dissection by their ears, nose, and throat (ENT) oncologist

    • Surgical exploration/sampling of all mucosal sites including ipsilateral wide field tonsillectomy and base of tongue resection. Additional biopsies or surgical excision at the surgeon's discretion. Any radiographic or clinically suspicious areas should be biopsied or removed. Bilateral neck dissection for high risk patients. Ipsilateral dissection only, for patients with contralateral cN0 necks and negative preoperative imaging
    • Final pathologic evaluation demonstrating all benign samplings without discernible primary
  • Documented smoking history
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 35 days prior to registration)
  • Platelet count >= 100,000/mm^3 (obtained =< 35 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (obtained =< 35 days prior to registration)
  • Creatinine =< 1.5 mg/dL or creatinine clearance >= 50 mL/min (obtained =< 35 days prior to registration)
  • Total or direct bilirubin < 2 x institutional upper limit of normal (ULN) (obtained =< 35 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x institutional ULN (obtained =< 35 days prior to registration)
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Able to provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

  • Any patient with positive retropharyngeal nodes on imaging

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • 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
  • 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
  • Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • History of connective tissue disorders such as scleroderma, rheumatoid arthritis, lupus, or Sjogren's disease
  • Prior history of radiation therapy to the affected site

Sites / Locations

  • Mayo Clinic in ArizonaRecruiting
  • Mayo Clinic in RochesterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (follow-up, observation)

Arm Description

Patients who have recurrence or progression during treatment or observation have medical charts are reviewed every 6 months for 5 years. Patients who complete adjuvant treatment are followed for observation 3 days after radiation therapy, 1 month after radiation therapy, every 3 months after radiation therapy for 2 years, every 6 months for 1 year, and then annually for 2 years.

Outcomes

Primary Outcome Measures

Primary local recurrence
Will be estimated by counting up the number of patients with an occult primary tumor within the pharyngeal axis or nodal recurrence in untreated neck and dividing by the total number of eligible patients.

Secondary Outcome Measures

Incidence of acute grade 3 or higher functional mucosal adverse events
Will characterize the acute grade 3 or higher functional mucosal adverse events (up to 1 month post-XRT) associated with mucosal sparing.
Overall survival (OS)
The distribution of OS will be estimated using the method of Kaplan-Meier.
Recurrence-free survival (RFS)
The distribution of RFS will be estimated using the method of Kaplan-Meier.
Distant metastasis rates
Change in swallowing function
To describe swallowing function changes (assessed via swallowing study) associated with transoral surgery and adjuvant mucosal sparing radiotherapy. Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic eversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al. Swallowing assessments will be completed at baseline, along with 3 and 12 months after the completion of protocol XRT. The swallowing questions will be explored descriptively to detect patterns and substantial changes over time. In addition, McNemar's tests (or Wilcoxon signed-rank tests) for paired samples will be used to see if the swallowing questions significantly change over time for each post-baseline time point. MBSImp scoring and the Penetration/aspiration scale scores will be assessed as well.
Incidence of acute adverse events
The maximum grade for each type of acute adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ adverse events, regardless of attribution to the study treatment.
Incidence of late adverse events
The maximum grade for each type of adverse event will be recorded for each patient for up to 2 years post-treatment, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ non-hematologic adverse events, regardless of attribution to the study treatment. Hematologic adverse events will not be followed closely long-term given that adjuvant treatment is only given for 1 month.

Full Information

First Posted
July 20, 2020
Last Updated
April 24, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04489212
Brief Title
Study of Mucosal Sparing Adjuvant Radiotherapy After Surgical Exploration in HPV+ Head and Neck Cancer of Unknown Primaries
Official Title
A Study of Mucosal Sparing Adjuvant Radiotherapy After Surgical Exploration in HPV + Head and Neck Cancer of Unknown Primaries (HNCUP)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2020 (Actual)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This early phase I trial evaluates the clinical outcome of mucosal sparing adjuvant radiotherapy after surgical exploration in HPV+ head and neck cancer of unknown primaries. The purpose of this research is to assess if radiation treatment to the neck only for tumors with unclear original locations after careful surgical evaluation will lead to historical rates of disease control while reducing side effects and toxicity from treatment.
Detailed Description
PRIMARY OBJECTIVE: I. To describe the rate of manifestation of an occult primary tumor in the pharyngeal axis or delayed nodal recurrence in a un-dissected and/or non-irradiated neck at 2 years after study registration in patients treated with mucosal sparing (and unilateral neck, if applicable) radiotherapy after resection using transoral surgery for head and neck cancer of unknown primaries (HNCUP). SECONDARY OBJECTIVES: I. To describe the rates and severity of acute and late toxicities and PEG dependence attributable to mucosal sparing radiotherapy after resection using transoral surgery by assessment of grade 3 or higher adverse events National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 criteria. II. To describe the overall survival, recurrence-free survival (manifestation of an occult primary in the pharyngeal axis, nodal recurrence in a treated (surgery/radiation therapy [RT]) neck, delayed lymph node metastasis in an untreated neck (surgery/RT), and distant failure associated with mucosal sparing radiotherapy. III. To describe swallowing function changes (assessed via swallowing study) associated with transoral surgery and adjuvant mucosal sparing radiotherapy. OUTLINE: Patients who have recurrence or progression during treatment or observation have medical charts reviewed every 6 months for 5 years. Patients who complete adjuvant treatment are followed for observation 3 days after radiation therapy, 1 month after radiation therapy, every 3 months after radiation therapy for 2 years, every 6 months for 1 year, and then annually for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Carcinoma of Unknown Primary, Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (follow-up, observation)
Arm Type
Experimental
Arm Description
Patients who have recurrence or progression during treatment or observation have medical charts are reviewed every 6 months for 5 years. Patients who complete adjuvant treatment are followed for observation 3 days after radiation therapy, 1 month after radiation therapy, every 3 months after radiation therapy for 2 years, every 6 months for 1 year, and then annually for 2 years.
Intervention Type
Other
Intervention Name(s)
Medical Chart Review
Other Intervention Name(s)
Chart Review
Intervention Description
Review of medical chart
Intervention Type
Other
Intervention Name(s)
Patient Observation
Other Intervention Name(s)
Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting
Intervention Description
Undergo observation
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
Primary local recurrence
Description
Will be estimated by counting up the number of patients with an occult primary tumor within the pharyngeal axis or nodal recurrence in untreated neck and dividing by the total number of eligible patients.
Time Frame
At 2 years
Secondary Outcome Measure Information:
Title
Incidence of acute grade 3 or higher functional mucosal adverse events
Description
Will characterize the acute grade 3 or higher functional mucosal adverse events (up to 1 month post-XRT) associated with mucosal sparing.
Time Frame
Up to 1 month post radiation therapy (XRT)
Title
Overall survival (OS)
Description
The distribution of OS will be estimated using the method of Kaplan-Meier.
Time Frame
From registration to death due to any cause, assessed up to 5 years
Title
Recurrence-free survival (RFS)
Description
The distribution of RFS will be estimated using the method of Kaplan-Meier.
Time Frame
From registration to the first of either disease recurrence, delayed lymph node metastasis in an untreated neck (contralateral), development of distant metastatic disease, or death, assessed up to 5 years
Title
Distant metastasis rates
Time Frame
Up to 2 years
Title
Change in swallowing function
Description
To describe swallowing function changes (assessed via swallowing study) associated with transoral surgery and adjuvant mucosal sparing radiotherapy. Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic eversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al. Swallowing assessments will be completed at baseline, along with 3 and 12 months after the completion of protocol XRT. The swallowing questions will be explored descriptively to detect patterns and substantial changes over time. In addition, McNemar's tests (or Wilcoxon signed-rank tests) for paired samples will be used to see if the swallowing questions significantly change over time for each post-baseline time point. MBSImp scoring and the Penetration/aspiration scale scores will be assessed as well.
Time Frame
Up to 5 years
Title
Incidence of acute adverse events
Description
The maximum grade for each type of acute adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ adverse events, regardless of attribution to the study treatment.
Time Frame
Up to 1 month post-XRT
Title
Incidence of late adverse events
Description
The maximum grade for each type of adverse event will be recorded for each patient for up to 2 years post-treatment, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ non-hematologic adverse events, regardless of attribution to the study treatment. Hematologic adverse events will not be followed closely long-term given that adjuvant treatment is only given for 1 month.
Time Frame
Up to 2 years post-XRT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients meet criteria for intensity-modulated proton therapy (IMPT) treatment for oropharyngeal cancer If IMPT is declined by patient's insurance, they can be treated with standard of care IMRT using the same applicable standard of care procedures outlined in the procedures manual Meet criteria for adjuvant chemotherapy (if applicable) Histological confirmation of human papillomavirus (HPV)+ squamous cell carcinoma as defined by neck node pathology. HPV positivity will be defined as positive staining for p16 and HPV deoxyribonucleic acid (DNA) in situ hybridization (ISH). (If discordant, ribonucleic acid [RNA] ISH will be run for confirmatory testing) Clinical stage T0 N1-N3 and confirmed pathologic stage T0 N1-N2 M0 (American Joint Committee on Cancer [AJCC] 8th edition) with one of the following risk factors: Lymph node >= 3 cm >= 2 positive lymph nodes Presence of extracapsular extension > 1 nodal level involved Absence of distant metastases on standard diagnostic workup, prior to registration (chest computed tomography [CT], chest x-ray [CXR], or positron emission tomography [PET]/CT) Able to undergo pre-operative Q-clear series PET/CT head/neck for diagnostic workup of occult primary and nodal disease Able to undergo transoral surgery and neck dissection by their ears, nose, and throat (ENT) oncologist Surgical exploration/sampling of all mucosal sites including ipsilateral wide field tonsillectomy and base of tongue resection. Additional biopsies or surgical excision at the surgeon's discretion. Any radiographic or clinically suspicious areas should be biopsied or removed. Bilateral neck dissection for high risk patients. Ipsilateral dissection only, for patients with contralateral cN0 necks and negative preoperative imaging Final pathologic evaluation demonstrating all benign samplings without discernible primary Documented smoking history Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 35 days prior to registration) Platelet count >= 100,000/mm^3 (obtained =< 35 days prior to registration) Hemoglobin >= 8.0 g/dL (obtained =< 35 days prior to registration) Creatinine =< 1.5 mg/dL or creatinine clearance >= 50 mL/min (obtained =< 35 days prior to registration) Total or direct bilirubin < 2 x institutional upper limit of normal (ULN) (obtained =< 35 days prior to registration) Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x institutional ULN (obtained =< 35 days prior to registration) Ability to complete questionnaire(s) by themselves or with assistance Able to provide written informed consent Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) Exclusion Criteria: Any patient with positive retropharyngeal nodes on imaging Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception 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 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 Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm History of connective tissue disorders such as scleroderma, rheumatoid arthritis, lupus, or Sjogren's disease Prior history of radiation therapy to the affected site
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel J Ma
Organizational Affiliation
Mayo Clinic in Rochester
Official's Role
Principal Investigator
Facility Information:
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
Samir H. Patel, 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
Daniel J. Ma, M.D.

12. IPD Sharing Statement

Learn more about this trial

Study of Mucosal Sparing Adjuvant Radiotherapy After Surgical Exploration in HPV+ Head and Neck Cancer of Unknown Primaries

We'll reach out to this number within 24 hrs