HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer

Overview

There is a strong radiobiological and economic rationale for hypofractionated radiation therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and tolerability of hypofractionated radiation therapy in the post-operative setting, and to determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of swallowing-related quality of life and to assess the toxicity and efficacy of hypofractionated radiation therapy compared to conventionally fractionated radiation therapy in the post-operative setting.

Full Title of Study: “HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Squamous Cell Carcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2027

Detailed Description

The trial will assess the effects of aggressive hypofractionated radiation therapy in patients with oral cavity, oropharynx, hypopharynx, or larynx cancer after surgical resection with pathology showing intermediate risk factors requiring post-operative radiation therapy without concurrent chemotherapy. During Phase 1, the maximum tolerated dose/fractionation and tolerability will be determined. During Phase 2, patients will be randomized between conventionally fractionated radiation therapy (6 weeks) vs. hypofractionated radiation therapy (3-4 weeks depending on Phase 1 results) to establish non-inferiority of hypofractionated radiation therapy.

Interventions

  • Radiation: Intensity-modulated Radiation Therapy (IMRT)
    • Patients will receive adjuvant radiation therapy using intensity-modulated radiation therapy (IMRT) within 8 weeks of surgical resection

Arms, Groups and Cohorts

  • Active Comparator: Conventionally fractionated radiotherapy
    • 60 Gy in 30 fractions, 5 fractions/week
  • Experimental: Hypofractionated radiotherapy
    • Dose and fractionation determined by Phase I: Level 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 Level -2: 50 Gy in 20 fractions, 5 fractions/week

Clinical Trial Outcome Measures

Primary Measures

  • Phase 1: Maximally tolerated dose of hypofractionated radiation therapy
    • Time Frame: 3 months
    • Dose and fractionation to be used for Phase 2
  • Phase 2: Swallowing-related patient-reported quality of life
    • Time Frame: 12 months
    • MD Anderson Dysphagia Inventory (MDADI) composite score

Secondary Measures

  • Clinician-reported acute toxicities
    • Time Frame: 1-3 months
    • CTCAE v5.0
  • Clinician-reported late toxicities
    • Time Frame: 3-24 months
    • CTCAE v5.0
  • Locoregional control
    • Time Frame: 12-24 months
  • Progression free survival
    • Time Frame: 12-24 months
  • Overall survival
    • Time Frame: 12-24 months
  • Swallowing-related patient-reported quality of life
    • Time Frame: 1-24 months
    • MD Anderson Dysphagia Inventory (MDADI)
  • Head and neck patient-reported quality of life
    • Time Frame: 1-24 months
    • University of Washington QOL questionnaire (UW-QOL)
  • Xerostomia-related patient-reported quality of life
    • Time Frame: 1-24 months
    • University of Michigan Xerostomia questionnaire (XQ)
  • General patient-reported quality of life
    • Time Frame: 1-24 months
    • EuroQol-5 dimensions (EQ-5D-5L)
  • Feeding tube dependence
    • Time Frame: 1-24 months
    • Defined as daily use of the feeding tube with ≥2 nutritional supplements per day

Participating in This Clinical Trial

Inclusion Criteria

Inclusion criteria will be the same for Phase I and Phase II.

1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx status post gross total resection with pathology showing one or more of the following intermediate risk factors: T3/4 disease, positive lymph node(s), close margin(s), perineural invasion, and/or lymphovascular invasion

2. Age ≥18 years

3. ECOG performance status 0-2

4. 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.

5. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.

6. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

Phase I:

1. Distant metastasis

2. Stage I and II glottic squamous cell carcinoma

3. High risk factors following surgical resection requiring concurrent chemotherapy: positive margin(s) and/or extranodal extension

4. Feeding tube dependence at baseline assessment.

5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer. For thyroid cancer, surgery may occur before or after treatment, provided all other eligibility criteria are met.

6. Prior invasive malignancy with an expected disease-free interval of less than 3 years

7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields

8. Subjects may not be receiving any other investigational agents for the treatment of the cancer under 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, and organ or autologous or allogeneic stem cell transplant

Phase II:

The exclusion criteria will be the same as Phase I except for feeding tube dependence. Patients who are feeding tube dependent are excluded from Phase I to accurately assess treatment associated toxicity affecting swallowing and oral intake. During Phase II, patients who are feeding tube dependent will be eligible to enroll and stratified at randomization.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Texas Southwestern Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Dominic Moon, Assistant Professor – University of Texas Southwestern Medical Center
  • Overall Contact(s)
    • Dominic Moon, MD, 214-645-8525, Dominic.moon@utsouthwestern.edu

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