INRT-AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy

• ClinicalTrials.gov Identifier: NCT03953976
• Recruitment Status: Completed
• First Posted: May 17, 2019
• Last Update Posted: February 28, 2024
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): David Sher, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: May 13, 2019
• First Posted Date: May 17, 2019
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: July 23, 2019
• Actual Primary Completion Date: November 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2021)

To determine the risk of solitary elective volume recurrence following elective volume reduction using INRT. [ Time Frame: 2 years ]

Definition: solitary means that the recurrence occurred without a preceding or synchronous in-field or distant recurrence

Original Primary Outcome Measures (submitted: May 15, 2019)

Crude risk of solitary elective volume recurrence (SEVR) following INRT, according to NCI's CTCAE v4.0 toxicity criteria. [ Time Frame: 2 years ]

Comparison of SEVR risks by p16 status and anatomic site

Current Secondary Outcome Measures (submitted: August 19, 2022)

• Comparison of SEVR risks by p16 status and anatomic site [ Time Frame: 2 years ]
• EORTC QLQ-C30 Summary score [ Time Frame: 36 months ]
  The EORTC QLQ-C30 Summary Score is calculated from the mean of 13 of the 15 QLQ-C30 scales. Patients rate overall health and quality of life.
• EORTC QLQ-C30 Physical and role functioning subscales [ Time Frame: 36 months ]
  Patients rate overall health and quality of life.
• EORTC HN35 Dry mouth and sticky saliva subscales [ Time Frame: 36 months ]
  Patients report to which extent they experience symptoms or problems during one week.
• MDADI global, emotional, functional and physical subscales [ Time Frame: 36 months ]
  Questionnaire asks for views about swallowing ability.
• EQ-5D global score (0-100) [ Time Frame: 36 months ]
  Patients describe health for current day regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
• Grade 3-4 acute and late toxicity [ Time Frame: 2 years ]
  According to NCI's CTCAE v4.0 toxicity criteria
• Gastrostomy placement and subsequent removal rate [ Time Frame: 2 years ]
  To estimate the rates gastrostomy dependence at 3, 6, 12 and 24 months following treatment with INRT.
• To characterize patient utilities following treatment with INRT. [ Time Frame: 2 years ]
  Average patient utilities (derived from EQ-5D) at baseline, 3, 6, 12, 18, 24 and 36 months from the end of treatment.
• To determine 2-year overall and progression-free survival following treatment with INRT [ Time Frame: 2 years ]
  Overall survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (LR, RR, or DM) or death.
• To describe the patterns-of-failure following INRT. [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: May 15, 2019)

• EORTC QLQ-C30 Summary score [ Time Frame: 36 months ]
  Patients rate overall health and quality of life.
• EORTC QLQ-C30 Physical and role functioning subscales [ Time Frame: 36 months ]
  Patients rate overall health and quality of life.
• EORTC HN35 Dry mouth and sticky saliva subscales [ Time Frame: 36 months ]
  Patients report to which extent they experience symptoms or problems during one week.
• MDADI global, emotional, functional and physical subscales [ Time Frame: 36 months ]
  Questionnaire asks for views about swallowing ability.
• EQ-5D global score (0-100) [ Time Frame: 36 months ]
  Patients describe health for current day regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: INRT-AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy
• Official Title: INRT- AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy Using Artificial Intelligence-Based Radiomics for Head and Neck Squamous Cell Carcinoma
• Brief Summary: Elective nodal irradiation has been a longstanding standard-of-care in the management of mucosal squamous cell carcinoma of the head and neck. Recent studies have suggested that reduced elective dose and volume may be a viable approach to improve toxicity. In this study, we are eliminating the elective neck treatment, focusing therapy on involved and suspicious nodes.
• Detailed Description: We recently completed and reported a successful study (INFIELD) using reduced elective dose (40 Gy) and volume (involved echelons + 1) for oropharynx and larynx cancer. In INRT-AIR (Involved Nodal Radiotherapy using AI-based Radiomics), we are eliminating the elective neck treatment altogether, using radiologic and radiomic-based criteria to focus treatment on the nodes themselves. Eligible patients include previously untreated patients with stage I-IVB oropharynx, larynx and hypopharynx cancer, excluding T1-2 glottic carcinoma. Patients requiring chemotherapy may receive cisplatin, cetuximab, or carboplatin-paclitexel.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Squamous Cell Carcinoma

Intervention

Radiation: Intensity modulated radiation therapy (IMRT)

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel). 6.5-7 weeks of radiotherapy or chemoradiotherapy

Study Arms

Experimental: PET-CT at 3 months and ENT evaluation

Treatment to the gross primary and nodal disease (70 Gy), with suspicious nodes treated to 66.5 Gy, all in 35 fractions. CT and PET-CT are required for nodal assessment. Restaging PET-CT must be performed between 11-14 weeks from the completion of treatment. The patient must see an otolaryngologist after the PET-CT to decide on post-treatment neck dissection per the surgeon's judgement. Patients will then be seen every 3 months (+/- 2 weeks) for the first year, and then at least every 6 months (+/-2 weeks) until the 36 month. Subsequent and intervening follow-up visits will be made per physician preference

Intervention: Radiation: Intensity modulated radiation therapy (IMRT)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 15, 2019): 67
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 22, 2024
• Actual Primary Completion Date: November 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
2. Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (< 2 nodes) is also allowable.
3. Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
4. Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
5. Age ≥ 18 years.
6. ECOG Performance Status 0-2

7. 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.

   7.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

   • Has not undergone a hysterectomy or bilateral oophorectomy; or
   • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Negative serum pregnancy test within 2 weeks before registration for women of childbearing potential.
9. Neck CT and/or neck MRI, and PET-CT (at least skull-to-thigh).
10. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

1. Distant metastasis.
2. Inability to undergo PET-CT.
3. Stage I and II glottic carcinoma.
4. Gross total excision of both the primary and nodal disease.
5. Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, 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 systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable
8. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
9. Subjects may not be receiving any other investigational agents.
10. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
11. 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
12. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
13. History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03953976
• Other Study ID Numbers: STU 2019-0711
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: David Sher, University of Texas Southwestern Medical Center
• Original Responsible Party: University of Texas Southwestern Medical Center
• Current Study Sponsor: University of Texas Southwestern Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David J Sher, MD, MPH; UT Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: February 2024