Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy

Official title

INVERT - Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy

Overview

To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)

Detailed description

Patients are assigned to either elective nodal irradiation (ENI), the current treatment paradigm, or involved nodal radiotherapy (INRT), the experimental treatment. INRT is more specifically targeting potentially cancerous nodes, identified using an AI program developed in-house. The hope is that this more specific targeting will decrease healthy tissue being irradiated, therefore decreasing potential side effects of the radiation treatment.

Patients are blinded during study participation.

Interventions

• Drug ENI using IMRT with or without chemotherapy
  This study is a phase II single-blinded randomized trial comparing standard ENI with involved nodal radiotherapy. INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)
• Radiation INRT
  INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)
• Radiation ENI
  ENI using IMRT with or without chemotherapy

Primary outcome measures

• The probability at two years: SEVR in INRT versus ENI patients [Time frame: 2 years]

Secondary outcome measures (3)

• Incidence of Acute Grade 2+ Dermatitis between ENI vs INRT arms [Time frame: Start of RT through 90 days post RT]
• Incidence of Grade 3+ Dysphagia between ENI vs INRT arms [Time frame: 2 years post RT]
• MDADI Quality of Life composite score [Time frame: 2 years post RT]

Eligibility criteria

Inclusion criteria

• Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
• 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.
• Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
• Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
• Age ≥ 18 years.
• ECOG Performance Status 0-2
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, 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.
• 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).
• Neck CT and/or neck MRI, and PET-CT
• Ability to understand and the willingness to sign a written informed consent.

Exclusion criteria

• Distant metastasis.
• Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast.
• Inability to undergo PET-CT.
• Stage I and II glottic carcinoma.
• Gross total excision of both the primary and nodal disease.
• 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.
• Prior invasive malignancy with an expected disease-free interval of less than 3 years.
• Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
• Subjects may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
• 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.
• History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• UT Southwestern Medical Center — Dallas

Publications

• Young S, Moon DH, Wang J, Chen L, Lin MH, Zhu L, Ahn C, Hughes R, Sher DJ. Involved nodal versus elective neck radiotherapy (INVERT) for head and neck squamous cell carcinoma: a prospective phase II randomized controlled trial protocol. BMC Cancer. 2026 May 11;26(1):815. doi: 10.1186/s12885-026-15904-8. PMID 42116021

Identifiers

NCT: NCT06477692 · STU-2024-0603 · 1R01CA251792-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗