Clinical Trials /

HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer

NCT04580446

Description:

This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to 60 Gy in 30 fractions) with concurrent weekly cisplatin.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer
  • Official Title: HYHOPE: Phase I Study of De-intensified Hypofractionated Radiation Therapy for Human Papilloma Virus-associated Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: STU 2020-1079
  • NCT ID: NCT04580446

Conditions

  • Human Papillomavirus-Related Carcinoma
  • Oropharyngeal Cancer

Purpose

This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to 60 Gy in 30 fractions) with concurrent weekly cisplatin.

Detailed Description

      Standard of care radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC)
      involves conventional fractionation delivered over a course of 7 weeks. Although
      hypofractionated RT (HFRT) delivering higher dose of RT each day over a shorter overall
      treatment time has been studied and adopted as standard of care in many disease sites
      including breast and prostate cancers, data on HFRT in HNSCC is limited.

      There is a strong radiobiological rationale for HFRT for HNSCC to decrease the overall
      treatment time and thus the effects of accelerated repopulation in this disease entity. In
      addition, if similar outcomes can be achieved with a reduced number of fractions, cost
      effectiveness of care can be improved while minimizing the disruption to the patient's
      personal and professional lives. A substantial decrease in treatment time may improve
      compliance and financial toxicity associated with the patient's oncologic treatment.

      The global COVID-19 pandemic is highlighting the health risk to society at large of having no
      viable alternative to a 7 week daily RT course for HNSCC, especially in the setting of
      compromised immune systems associated with concurrent chemotherapy frequently used in this
      patient population. Thus, the study of HFRT for HNSCC is both timely and potentially paradigm
      changing for practices across the United States.

      The incidence of human papilloma virus (HPV)-associated oropharynx cancer is increasing in
      the United States, now accounting for 70-80% of all oropharynx cancers. It has a favorable
      prognosis vs. non-HPV-associated cancers and studies are ongoing to determine the best
      strategy to de-intensified therapy while maintaining good oncologic outcomes.

      The purpose of this single-arm Phase I study is to assess the tolerability and signal for
      efficacy of de-intensified HFRT for favorable HPV-associated oropharynx cancer.
      De-intensification will be achieved in two ways. First, the equivalent biologically effective
      dose (BED) of HFRT used on trial will be 60 Gy of conventionally fractionationated RT (vs.
      the current standard of care of 70 Gy). Second, the elective nodal volume irradiated will be
      limited to involved nodal levels and one immediately adjacent level (vs. the current standard
      of care of entire bilateral neck nodal regions). Patients will complete RT in 15 fractions (3
      weeks) with concurrent weekly cisplatin on dose level 0, and if well tolerated, escalate to
      level 1 delivering RT in 12 fractions (3 weeks). If a 3-week regimen is not well-tolerated, a
      20 fraction regimen will be used on dose level -1.
    

Trial Arms

NameTypeDescriptionInterventions
Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2)ExperimentalLevel 1: 44.4 Gy in 12 fractions, 4 fractions/week Level 0: 46.5 Gy in 15 fractions, 5 fractions/week Level -1: 52 Gy in 20 fractions, 5 fractions/week

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Pathologically-proven diagnosis of T1-3 (up to 6 cm), N0-2 (AJCC 8th edition) p16
                 positive squamous cell carcinoma of the oropharynx (except T1-2N0 as noted in the
                 exclusion criteria)
    
              2. ≤10 pack-year smoking history and not actively smoking
    
              3. Age ≥18 years
    
              4. ECOG performance status 0-2
    
              5. Women of child-bearing potential and men must agree to use adequate contraception
                 (hormonal or barrier method of birth control; abstinence) prior to study entry, for
                 the duration of study participation, and for 90 days following completion of therapy.
                 Should a woman become pregnant or suspect she is pregnant while participating in this
                 study, she should inform her treating physician immediately.
    
              6. Negative serum or urine pregnancy test within 2 weeks before registration for women of
                 childbearing potential.
    
              7. Ability to understand and the willingness to sign a written informed consent.
    
            Exclusion Criteria:
    
              1. Distant metastasis
    
              2. T1-2N0 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx
                 (candidates for definitive RT alone or surgery alone)
    
              3. Inability to receive concurrent weekly cisplatin due to comorbid conditions
    
              4. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx,
                 and hypopharynx except for low- and intermediate-risk prostate cancer and
                 well-differentiated thyroid cancer. For prostate cancer, patient should not be
                 receiving active treatment. For thyroid cancer, thyroid surgery may occur before or
                 after radiation treatment, provided all other eligibility criteria are met.
    
              5. Prior invasive malignancy with an expected disease-free interval of less than 3 years
    
              6. Prior radiotherapy to the region of the study cancer that would result in overlap of
                 radiation fields
    
              7. Subjects may not be receiving any other investigational agents for the treatment of
                 the cancer under study.
    
              8. History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to the chemotherapy agents in this study
    
              9. 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, in the opinion of the
                 investigator, would limit compliance with study requirements
    
             10. Subjects must not be pregnant or nursing due to the potential for congenital
                 abnormalities and the potential of this regimen to harm nursing infants.
    
             11. History of severe immunosuppression, including HIV, organ or autologous or allogeneic
                 stem cell transplant, or active immunosuppressive medication at the time of enrollment
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximally tolerated dose and fractionation of hypofractionated radiation therapy
    Time Frame:3 months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Clinician-reported acute toxicities
    Time Frame:0-3 months
    Safety Issue:
    Description:CTCAE v5.0
    Measure:Clinician-reported late toxicities
    Time Frame:3-12 months
    Safety Issue:
    Description:CTCAE v5.0
    Measure:Locoregional control
    Time Frame:12 months
    Safety Issue:
    Description:
    Measure:Progression free survival
    Time Frame:12 months
    Safety Issue:
    Description:
    Measure:Swallowing-related patient-reported quality of life
    Time Frame:1-12 months
    Safety Issue:
    Description:MD Anderson Dysphagia Inventory (MDADI): 20-100, higher scores mean better quality of life
    Measure:Head and neck patient-reported quality of life
    Time Frame:1-12 months
    Safety Issue:
    Description:University of Washington QOL questionnaire (UW-QOL): 0-100, higher scores mean better quality of life
    Measure:Xerostomia-related patient-reported quality of life
    Time Frame:1-12 months
    Safety Issue:
    Description:University of Michigan Xerostomia questionnaire (XQ): 0-100, higher scores mean worse quality of life
    Measure:General patient-reported quality of life
    Time Frame:1-12 months
    Safety Issue:
    Description:EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life
    Measure:Feeding tube dependence
    Time Frame:1-12 months
    Safety Issue:
    Description:Dependence on tube feeds defined as daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Texas Southwestern Medical Center

    Trial Keywords

    • Radiation Dose Hypofractionation

    Last Updated

    January 7, 2021