Clinical Trials /

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

NCT04489212

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: MC1974
  • SECONDARY ID: NCI-2020-05152
  • SECONDARY ID: MC1974
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04489212

Conditions

  • 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

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (follow-up, observation)ExperimentalPatients 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.

    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)
    
              -  Pathologic stage T0 N1-N3 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Primary local recurrence
    Time Frame:At 2 years
    Safety Issue:
    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.

    Secondary Outcome Measures

    Measure:Incidence of acute grade 3 or higher functional mucosal adverse events
    Time Frame:Up to 1 month post radiation therapy (XRT)
    Safety Issue:
    Description:Will characterize the acute grade 3 or higher functional mucosal adverse events (up to 1 month post-XRT) associated with mucosal sparing.
    Measure:Overall survival (OS)
    Time Frame:From registration to death due to any cause, assessed up to 5 years
    Safety Issue:
    Description:The distribution of OS will be estimated using the method of Kaplan-Meier.
    Measure:Recurrence-free survival (RFS)
    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
    Safety Issue:
    Description:The distribution of RFS will be estimated using the method of Kaplan-Meier.
    Measure:Distant metastasis rates
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Change in swallowing function
    Time Frame:Up to 5 years
    Safety Issue:
    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.
    Measure:Change in swallowing function
    Time Frame:Up to 5 years
    Safety Issue:
    Description:To describe swallowing function changes (assessed via swallowing study) associated with 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.
    Measure:Change in swallowing function
    Time Frame:Up to 5 years
    Safety Issue:
    Description:To describe swallowing function changes (assessed via swallowing study) 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.
    Measure:Incidence of acute adverse events
    Time Frame:Up to 1 month post-XRT
    Safety Issue:
    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.
    Measure:Incidence of late adverse events
    Time Frame:Up to 2 years post-XRT
    Safety Issue:
    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.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Mayo Clinic

    Last Updated

    July 23, 2020