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

NCT ID: NCT06477692

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-14
• Study Completion Date: 2028-07-01

Brief Summary

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard radiotherapy with elective neck irradiation (ENI)

The elective neck dose is 56 Gy in 35 fractions Lymph nodes measuring 17 mm or greater in any dimension, or showing FDG above adjacent blood pool, may receive 63 Gy in 35 fractions per physician discretion.The elective neck field is determined by the primary site.

The Oropharynx:

Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-IV, RP at discretion of physician For ipsilateral tonsil decision-making, see 4.1.1.6.3

The Larynx:

Node-positive side: Levels IB-V Node-negative side: Levels II-IV Subglottic extension: Level VI

Hypopharynx:

Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-V and RP nodes Pyriform sinus involvement: Level VI

Group Type: ACTIVE_COMPARATOR

ENI using IMRT with or without chemotherapy

Intervention Type: DRUG

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)

ENI

Intervention Type: RADIATION

ENI using IMRT with or without chemotherapy

Involved and suspicious lymph node delineation and targeting

After the involved and suspicious nodes are contoured, the physician will contour remaining nodes that are present on more than one CT slice and submit them to the AI-Radiomics module for assessment.The nodal gross tumor volume (GTVn, GTVns and GTVnps for involved, suspicious nodes or potentially suspicious) will be contoured on the planning CT, using radiographic and clinical information to define its extent. The total dose for GTVns is 63 Gy in 35 fractions, and the total dose for GTVnps is 56 Gy in 35 fractions. For lymph nodes identified as potentially suspicious by the AI- Radiomics module that are outside of the expected primary draining zone, physicians may not treat the lymph node if the module assesses its estimation uncertainty as greater than 50%.

Group Type: EXPERIMENTAL

ENI using IMRT with or without chemotherapy

Intervention Type: DRUG

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)

INRT

Intervention Type: RADIATION

INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)

Interventions

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)

Intervention Type: DRUG

INRT

INRT using intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin- paclitaxel)

Intervention Type: RADIATION

ENI

ENI using IMRT with or without chemotherapy

Intervention Type: RADIATION

Other Intervention Names

cisplatin, cetuximab, or carboplatin- paclitaxel)

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David Sher

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Sher, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sarah Neufeld

Role: CONTACT

Sarah.hardee@utsouthwestern.edu

214-645-8525

Liliana Robles

Role: CONTACT

liliana.robles@utsouthwestern.edu

214-645-8525

Facility Contacts

Sarah Neufeld, MS

Role: primary

Other Identifiers

1R01CA251792-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2024-0603

Identifier Type: -

Identifier Source: org_study_id