Multi-Site Trial of Navigation vs Treatment as Usual to Improve Initiation of Timely Adjuvant Therapy (ENDURE)

A Stepped Wedge Cluster Randomized Trial Comparing a Navigation-Based Multilevel Intervention With Treatment as Usual to Improve Initiation of Timely Postoperative Radiation Therapy in Adults With Head and Neck Cancer

The goal of this clinical trial is to compare the effectiveness of a navigation-based multilevel intervention (ENDURE) with treatment as usual (TAU) to improve the initiation of guideline-adherent postoperative radiation therapy among patients with head and neck cancer. The main questions the trial aims to answer are:

1. Does ENDURE improve initiation of timely PORT relative to treatment as usual?
2. What are the mechanisms through which ENDURE improves timeliness to treatment?
3. What are the barriers and facilitators to the implementation of ENDURE into routine clinical care?

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Oropharynx Cancer; Oral Cavity Cancer; Larynx Cancer
• Intervention / Treatment: Behavioral: ENDURE

Detailed Description

In this hybrid type 1 effectiveness-implementation study, the investigators will conduct a stepped-wedge cluster randomized trial with cancer centers (n=4; 484 patients) randomized to sequentially deliver treatment as usual (TAU) then ENDURE to patients with head and neck cancer undergoing surgery and postoperative radiation therapy (PORT). The trial will assess the effect of ENDURE vs TAU on improving initiation of timely PORT (primary objective) and the underlying mechanisms of ENDURE (secondary objective). The investigators will concurrently conduct a mixed-methods study with quantitative measures of implementation outcomes and qualitative data about implementation determinants from semi-structured interviews with key stakeholders and site visits (exploratory objective).

• Study Type: Interventional
• Enrollment (Estimated): 532
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Evan M Graboyes, MD, MPH; Phone Number: 843-792-0719; Email: graboyes@musc.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in St. Louis
      • Contact: Ryan Jackson, MD; Phone Number: 314 362 8641; Email: jackson.ryan@wustl.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Russel R Kahmke, MD, MMCi
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Evan Graboyes, M.D., MPH, FACS; Phone Number: (843) 792-0719; Email: graboyes@musc.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Vlad C Sandulache, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age >/= 18 years
2. Squamous cell carcinoma (SCC) (or histologic variant) of the oral cavity, oropharynx, hypopharynx, larynx, unknown primary, paranasal sinuses, or nasal cavity
3. American Joint Committee on Cancer (AJCC) 8th edition clinical T3-4 or >N1 SCC of the oral cavity, oropharynx, hypopharynx, larynx, paranasal sinuses, nasal cavity, or unknown primary.
4. No history of radiation therapy for treatment of HNSCC in the definitive or adjuvant settings that would, at the discretion of the enrolling clinician, affect the patient's need for adjuvant RT.
5. Plan for curative intent surgery at one of the participating centers
6. Plan for PORT (regardless of whether it is at the surgical center) with or without concurrent chemotherapy following curative intent surgery based on the expectation of at least one of the following adverse features on final pathologic evaluation: pT3 or pT4 primary, N1 or greater nodal disease, perineural invasion (PNI), or lymphovascular invasion (LVI).

Exclusion Criteria:

1. Inability to speak or read English or Spanish.
2. Severe mental illness that would prevent trial participation.
3. HPV-positive OPC or unknown primary SCC staged as cT1-2N1 with a single ipsilateral LN < 3 cm
4. Synchronous untreated malignancy expected to impact life expectancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Treatment As Usual; Treatment as usual at each site consists of standard of care clinical practices
Experimental: ENDURE; ENDURE is a theoretically-informed, navigation-based, multilevel intervention targeting barriers to timely, guideline-adherent PORT.	Behavioral: ENDURE; ENDURE provides patient education through the ENDURE Patient Resource Guide and social support by linking patients to community resources (patient-level), standardizes discussions about expectations for PORT and clinical documentation to enhance communication and care coordination within and across interprofessional cancer teams (team-level), and implements referral tracking across fragmented health systems (organization-level). To facilitate care coordination, ENDURE modifies existing standard of care patient navigation (an evidence-based intervention that addresses barriers to timely cancer care) by adding PORT-focused navigation at three key care transitions: into the cancer care system; from inpatient to outpatient after surgery; and from the surgical team to the radiation oncology team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initiation of Timely PORT	The initiation of PORT > 6 weeks (42 days) following definitive surgery for HNSCC.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-PORT	The number of days from the date of definitive surgery for HNSCC to the date of initiation of PORT.	4 months
Pre-Surgical consultation with radiation oncology	Consultation with a treating radiation oncologist prior to definitive surgery for HNSCC.	1 month
Pre-radiation therapy dental extractions	The removal of indicated carious/non-restorable teeth prior to or during the surgery for HNSCC.	1 month
Time to postoperative scheduling with radiation oncology	The time from definitive surgery to the placement of the postoperative referral (or follow-up appointment) with the treating radiation oncologist.	3 months
Time to postoperative appointment with radiation oncology	Time from definitive surgery to the attendance at an appointment with the treating radiation oncologist.	3 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Evan M Graboyes, MD, MPH, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Carcinoma, Squamous Cell; Laryngeal Diseases; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms
• Other Study ID Numbers: Pro00123953; R01CA282165 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Below are the key elements of the data sharing plan as outlined in the NIH Policy for Data Management and Sharing:

Research materials will include: (1) self-report measures from patients; (2) clinical data from the electronic medical record; (3) audio recordings and transcriptions of interviews from stakeholders; and (4) field notes from direct observations of the delivery of ENDURE at each site. Data will be raw or minimally processed. The investigators plan to use REDCap for data capture and management of the clinical and self-report measure data and NVivo for management of the qualitative data. REDCap data dictionaries can be distributed for reuse. The final data dictionaries have not been developed. Scientific data and metadata will be generated, preserved, and shared using NIH common data elements. Scientific data and metadata arising from the project will be uploaded to openICPSR, a self-publishing repository for social, behavioral, and health sciences research data.

• IPD Sharing Time Frame: Data will be shared no later than the time of a publication of findings of the trial's primary endpoint in a peer-reviewed journal.
• IPD Sharing Access Criteria: All data sharing will comply with privacy and confidentiality protections such as the NIH Certificate of Confidentiality and applicable laws, regulations, and policies governing data derived from human participants.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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