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

INRT- AIR: A Prospective Phase II Study of Involved Nodal Radiation Therapy Using Artificial Intelligence-Based Radiomics for Head and Neck Squamous Cell Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Intensity modulated radiation therapy (IMRT)

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
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the risk of solitary elective volume recurrence following elective volume reduction using INRT.	Definition: solitary means that the recurrence occurred without a preceding or synchronous in-field or distant recurrence	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: David J Sher, MD, MPH, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: May 13, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: STU 2019-0711

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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