Clinical trial NCT03953976: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-05-17
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To determine the risk of solitary elective volume recurrence following elective volume reduction using INRT.
timeFrame: 2 years
Secondary outcomes:
measure: Comparison of SEVR risks by p16 status and anatomic site
timeFrame: 2 years
measure: EORTC QLQ-C30 Summary score
timeFrame: 36 months
measure: EORTC QLQ-C30 Physical and role functioning subscales
timeFrame: 36 months
measure: EORTC HN35 Dry mouth and sticky saliva subscales
timeFrame: 36 months
measure: MDADI global, emotional, functional and physical subscales
timeFrame: 36 months
measure: EQ-5D global score (0-100)
timeFrame: 36 months
measure: Grade 3-4 acute and late toxicity
timeFrame: 2 years
measure: Gastrostomy placement and subsequent removal rate
timeFrame: 2 years
measure: To characterize patient utilities following treatment with INRT.
timeFrame: 2 years
measure: To determine 2-year overall and progression-free survival following treatment with INRT
timeFrame: 2 years
measure: To describe the patterns-of-failure following INRT.
timeFrame: 2 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Dallas
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: David J Sher, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: