Navigation vs Usual Care for Timely Adjuvant Therapy for Patients With Locally Advanced HNSCC

Study Overview
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Brief Summary
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Head and neck cancer squamous cell carcinoma (HNSCC) is a disease with poor survival, especially for African Americans, despite intense treatment including surgery, radiation, and chemotherapy. Delays between surgery and the start of postoperative radiation therapy (PORT) are common, cause excess mortality, and contribute to worse survival in African Americans. Our research team has developed NDURE (Navigation for Disparities and Untimely Radiation thErapy), a novel theory-based patient navigation (PN) intervention to decrease delays and racial disparities starting PORT. In this single-site, open label, parallel-group, randomized controlled trial of adults with surgically-managed, locally advanced HNSCC, will be randomized to NDURE versus usual care to assess the preliminary clinical impact of NDURE on delays and racial disparities starting PORT after surgery for HNSCC. The investigators will collect information about the rate of PORT delay, racial disparities in the rate of PORT delay, and completion rate of key cancer care processes. Participants will also complete validated questionnaires at baseline and post-intervention to understand the theoretical constructs underlying NDURE . Post-intervention, patients and providers will undergo interviews to obtain in-depth understanding of the content, format, timing, and delivery of NDURE to optimize the intervention in preparation for a future multi-site study. NDURE could provide the first effective intervention to improve the delivery of timely, equitable PORT after HNC surgery, thereby improving survival for patients with HNC, decreasing racial disparities in mortality, and developing new standards of clinical care.

Detailed Description
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Design: The study design is a Single-Site, Parallel-Group, Randomized-Controlled Trial of Navigation Versus Usual Care for The Management of Delays and Racial Disparities Starting Postoperative Radiation Therapy in Adults with Surgically-Managed, Locally Advanced Head and Neck Squamous Cell Carcinoma Following screening and informed consent, sociodemographic, oncologic and symptom data will be prospectively gathered about participants from validated questionnaires and the electronic medical record (EMR). Participants will then be randomized to 3-sessions of the navigation intervention (NDURE; Navigation for Disparities and Untimely Radiation thErapy) or usual care (UC) and followed until the start of postoperative radiation therapy (PORT) following surgery for head and neck squamous cell carcinoma (HNSCC). Measures of PORT delay, racial disparities in PORT delay, key cancer care delivery processes, and theoretical constructs underlying PORT will be evaluated. Treatment Allocation: Upon enrollment, participants will be randomized 1:1 to NDURE or UC using a stratified randomization design with strata defined by race (white, African American [AA]) and location of radiation facility (Medical University of South Carolina ([MUSC], non-MUSC) because of the known association of these variables with PORT delay. Delivery of intervention: NDURE is a theory-based, multi-level PN intervention consisting of three in-person, clinic-based sessions of manualized PN with multiple intervention components that target system- (care coordination), interpersonal- (social support), and individual- (Health Belief Model; perceived susceptibility, severity, barriers, self-efficacy) level health behavior theoretical constructs to reduce barriers to care, increase HNSCC care delivery, and improve clinical outcomes (timely, equitable PORT). NDURE will be delivered from surgical consultation to PORT initiation ( 3 months). The NDURE intervention consists of: Navigation Sessions, the Navigator Manual, the Navigator Patient Guide, structured EMR documentation, weekly conferences to facilitate care coordination, real-time patient tracking, and multidisciplinary reporting. The three in-person NDURE navigation sessions, which are expected to take 30-60 minutes each, will coincide with the presurgical consult, hospital discharge, and 1st postoperative clinic visit, time points chosen to facilitate case identification and coordination across key care transitions. Contact beyond the three prescribed in-person sessions will occur with a frequency and modality (e.g. text message, email, etc.) dictated by patient and navigator need. During the first in-person session, the navigator will 1) elicit barriers and facilitators to timely PORT from the patient, caregiver, and provider, 2) develop the personalized barrier reduction plan (BRP), review it with the patient, caregiver, and provider, and 3) implement the BRP. At the two subsequent in-person sessions, the navigator will review and update the BRP in an iterative, dynamic fashion, identifying new barriers and systematically tracking resolution of prior barriers until the start of PORT. The Navigator Manual provides a structured resource to guide intervention delivery and enhance reproducibility. The Patient Guide is 1) literacy-level appropriate, 2) personalized for each patient's care pathway and BRP, 3) updated longitudinally as the patient progresses along the cancer continuum, and 4) available to patients in print and/or electronically via the patient portal in the EMR. UC consists of oncology visits with provider-led discussion about the referrals needed to start PORT. Expected Effect Size and Power Calculation: Power and sample size calculations were performed using PASS version 08.0.13, Inequality Tests for Two Independent Proportions. The primary endpoint for this pilot RCT is the rate of PORT delay, defined by NCCN Guidelines as PORT initiation > 6 weeks following surgery. Our primary objective is to compare PORT delay rates between the NDURE and UC arms. Patients (n=150) will be randomized 1:1 to NDURE or UC using a stratified randomization design with strata defined by race (white or AA) and location of radiation facility (MUSC or not MUSC). Furthermore, to facilitate evaluation of PORT delay rates in racial subgroups, the investigators will oversample AAs for a final sample size of 50 white and 25 AA patients in each arm. The investigators assume the rate of PORT delay in the usual care arm will be 45% and target an absolute reduction of 20% for a PORT delay in the navigation arm of 25%. This effect size is clinically significant and is a realistic goal given published rates of improvement in similar (non-randomized) interventions. Seventy-five patients in each arm yields 83% power to detect a 20% reduction in PORT delay (45% versus 25%) based on a two-sided Mantel-Haenszel test of two independent proportions assuming a two-sided α = 0.1. Our choice of the Mantel-Haenszel test to compare proportions is based on the trial's stratified design. Our selection of α = 0.1 and 1 - β = 0.8 is based on the desire to emphasize power over type I error at this early stage of development (single institution phase II trial) to ensure follow-up on promising interventions. The investigators therefore consider our trial to be appropriately and rigorously designed to detect a clinically meaningful reduction in PORT delay. Statistical Methods of Analysis: Graphical displays and descriptive statistics for sociodemographic, oncologic, and baseline symptom severity characteristics will be used to examine patterns and summarize data for each arm. The percentage of patients who start PORT within 6 weeks of surgery (the primary outcome measure) and corresponding 95% confidence interval (CI) will be calculated for both arms and for white and AA subgroups within each arm separately. The rate of PORT delay will be compared between arms using a Mantel-Haenszel test of two proportions, with strata defined by race and location of radiation facility. The investigators will analyze time to PORT as a continuous variable and estimate median time to PORT for each arm and for racial subgroups within each arm using Kaplan-Meier curves with Greenwood variance estimation to construct the corresponding 95% CIs. The investigators will estimate the hazard ratio comparing the two arms using Cox proportional hazards regression controlling for the stratification variables. The investigators will compare time to PORT between intervention arms using a stratified log-rank test. For other secondary endpoints, data will be summarized using frequency and percent for categorical variables and using mean, median, standard deviation, IQR and range for continuous variables. The investigators will also construct 95% CIs to provide a measure of uncertainty in estimated proportions and means. Comparisons between trial arms of other secondary endpoints will be performed using t-tests and chi-square tests, or Wilcoxon rank sum and Fisher's exact tests as appropriate. Baseline and post-intervention values of variables measuring the theoretical constructs underlying NDURE (i.e. care coordination, self-efficacy in cancer care, interpersonal support, and knowledge) will be compared using Wilcoxon sign rank tests. Comparisons between arms of the change in scores will be conducted using Wilcoxon rank sum tests.

Official Title
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Parallel-Group, Randomized-Controlled Trial of Navigation Vs Usual Care for The Management of Delays and Racial Disparities Starting Adjuvant Therapy in Adults With Surgically-Managed, Locally Advanced HNSCC (NDURE 2.0)

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Behavioral: NDURE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient and disease characteristics Age > 18 years at the time of screening Histologically or pathologically confirmed invasive SCC (or histologic variant) of the oral cavity, oropharynx (p16 positive, negative, or unknown), hypopharynx, larynx, unknown primary, paranasal sinuses, or nasal cavity. a. In situations in which the patient fulfills all other inclusion criteria but the biopsy shows SCC in-situ or moderate/severe dysplasia (without definitive evidence of invasive SCC), but the patient is scheduled to undergo curative intent surgery by the treating oncologic surgeon due to clinical suspicion of invasive SCC, the diagnosis of SCC-in situ or moderate/severe dysplasia is sufficient to full the pathologic diagnosis enrollment criterion. American Joint Committee on Cancer (AJCC) clinical stage grouping III-IV (8th edition) for patients with SCC of the oral cavity, p16-negative oropharynx, hypopharynx, larynx, paranasal sinuses, and nasal cavity; or AJCC clinical stage grouping III-IV (7th edition) for patients with p16-positive SCC of the oropharynx or unknown primary. At screening, AJCC clinical stage grouping should be determined based on a combination of physical exam, diagnostic evaluation with cross sectional imaging of the neck (computerized tomography (CT) and/or magnetic resonance imaging (MRI)) and/or 18-F-fluoro-deoxyglucose positron emission tomography (FDG PET) CT within 30 days In situations in which the patient fulfills all other inclusion criteria but the biopsy shows SCC in-situ or moderate/severe dysplasia (without definitive evidence of invasive SCC), but would otherwise have an appropriate clinical stage grouping as defined in criterion 5, the diagnosis of SCC-in situ or moderate/severe dysplasia is sufficient to full the staging enrollment criterion. No prior exposure to radiation therapy, with or without concurrent chemotherapy, for treatment of HNSCC in the definitive or adjuvant therapy settings Surgery and adjuvant therapy eligibility Plan for curative intent surgery at MUSC a. At screening, plan for curative intent surgical resection of the HNSCC at MUSC must be deemed likely by the treating surgeon and/or multidisciplinary tumor board, which must include a fellowship-trained head and neck oncologic surgeon Plan for PORT (at MUSC or non-MUSC) with or without concurrent chemotherapy following curative intent surgery a. At screening, plan for adjuvant therapy following curative intent surgical resection of the HNSCC at MUSC must be deemed likely by the treating surgeon and/or multidisciplinary tumor board, which must include a fellowship-trained head and neck oncologic surgeon, based on the clinical expectation of at least one of the following adverse features on final pathologic evaluation: extranodal extension (ENE), pT3 or pT4 primary, N2 or N3 nodal disease, nodal disease in levels IV or V, perineural invasion (PNI), or lymphovascular invasion (LVI) Exclusion Criteria: Self-identified Hispanic ethnicity Presence of cognitive impairment that precludes participation Synchronous untreated malignancy Failure to undergo curative intent surgery at MUSC Lack of indication for PORT (with or without concurrent chemotherapy) per National Comprehensive Cancer Network (NCCN) Guidelines based on the presence of at least one of the following adverse features on final pathologic evaluation: ENE, positive margin, pT3 or pT4 primary, N2 or N3 nodal disease, nodal disease in levels IV or V, PNI, or LVI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NDURE<br>NDURE is a theory-based, multi-level patient navigation (PN) intervention consisting of three in-person, clinic-based sessions of manualized PN with multiple intervention components that target system-(care coordination), interpersonal-(social support), and individual- (health belief model [HBM]; perceived susceptibility, severity, barriers, self-efficacy) level health behavior theoretical constructs to reduce barriers to care, enhance HNSCC care delivery, and improve clinical outcomes (timely, equitable PORT). NDURE will be delivered from surgical consultation to PORT initiation ( 3 months). The three in-person NDURE navigation sessions, which are expected to take 30-60 minutes each, will coincide with the presurgical consult, hospital discharge, and 1st postoperative clinic visit, time points chosen to facilitate case identification and coordination across key care transitions. | Behavioral: NDURE<br>* NDURE is a theory-based, multi-level Patient Navigation (PN) intervention consisting of three in-person, clinic-based sessions of manualized PN with multiple intervention components that target system- (care coordination), interpersonal- (social support), and individual- (Health Belief Model; perceived susceptibility, severity, barriers, self-efficacy) level health behavior theoretical constructs to reduce barriers to care, improve cancer care delivery, and improve clinical outcomes (timely, equitable PORT). NDURE will be delivered from surgical consultation to PORT initiation ( 3 months).<br>|
| No Intervention: Usual Care<br>UC consists of discussions about the indications, risks/benefits/alternative, Guidelines, timing, and logistical details of adjuvant therapy. These discussions will be administered according to practice patterns of the involved providers. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay Initiating Postoperative Radiation Therapy (PORT) | Initiation of PORT > 6 weeks after surgery | 6 weeks after surgery | 
| Time interval between surgery and the start of PORT | Time, in days, between the date of definitive surgical resection to the initiation of radiation therapy | 12 weeks from the date of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barriers Resolution Rate | The number of barriers identified by the navigator that are resolved during the NDURE intervention, as determined by the navigator log | Post-intervention (3 months) | 
| Unresolved Barriers | The number of barriers identified by the navigator that are not resolved during the NDURE intervention, as determined by the navigator log. | Post-intervention (3 months) | 
| Percent of Patients with Pre-surgical Radiation Consultation | The measures assesses the performance (or lack thereof) of a care delivery process (Pre-Surigcal Radiation Consultation) for patients with HNSCC. The measure is evaluated as performed if the patient attends a consultation with a radiation oncologist (at MUSC or elsewhere) prior to surgery to discuss RT in the definitive or adjuvant setting | 3 months | 
| Percent of Patients with Pre-Radiation Therapy Dental Extractions | The measures assesses the performance (or lack thereof) of a care delivery process (Pre-Radiation Therapy Dental Extractions) for patients with HNSCC. The measure is evaluated as performed if the patient has extraction of his/her indicated teeth prior to discharge from the index hospitalization for the definitive surgical procedure. Patients who are edentulous are not evaluable for this measure. | 3 months | 
| Percent of Patients with Surgery to Pathology Report </= 7 days | The measures assesses the performance (or lack thereof) of a care delivery process (Surgery to Pathology Report </= 7 days) for patients with HNSCC. The measure is evaluated as performed if the pathology report from the definitive surgical procedure is produced within the EMR within 7 calendar days of the definitive surgical procedure. Addenda to the pathology report at the request of the HNSCC team (e.g. tumor p16 status) are not counted in this measure. | 3 months | 
| Percent of Patients with Surgery to PORT Referral </= 10 days | The measures assesses the performance (or lack thereof) of a care delivery process (Surgery to PORT Referral </= 10 days) for patients with HNSCC. The measure is evaluated as performed if the a referral for PORT is placed, at MUSC or elsewhere, within 10 calendar days of the definitive surgical procedure. | 3 months | 
| Percent of Patients with RT Referral to Consult </= 10 days | TThe measures assesses the performance (or lack thereof) of a care delivery process (Surgery to PORT Referral </= 10 days) for patients with HNSCC. The measure is evaluated as performed if a patient is evaluated in consultation at a postoperative consultation with a radiation oncologist within 10 calendar days of the referral being placed (or postoperative appointment being scheduled in cases in which care has been established and the return visit is no longer a consultation). The consultation may occur in the clinic or the hospital depending upon clinical circumstances. | 3 months | 
| Percent of Patients with RT Consult to Initiation </= 21 days | The measures assesses the performance (or lack thereof) of a care delivery process (RT Consult to Initiation </= 21 days) for patients with HNSCC. The measure is evaluated as performed if PORT is initiated within 21 calendar days of the patient being evaluated by a radiation oncologist for PORT. | 3 months | 
| Care Transition Measure-15 (CTM-15) Score | A validated, psychometrically sound 15-item, unidimensional measure of care transitions across the healthcare system that is consistent with the concept of patient-centeredness and useful from an organization perspective for the purpose of performance measurement and quality improvement. Higher scores reflect higher levers of care integration and coordination | Post-intervention (3 months) | 
| Change from Baseline in Interpersonal Support Evaluation List-12 Score | A validated, 12-item assessment of three domains of interpersonal support that has been used to assess support in prior PN studies. Items are rated on a 4-point Likert scale with higher scores indicating more support | Change from baseline to post-intervention (3 months) | 
| Change from Baseline in Perceived Susceptibility Scale Score | A modified version of a validated 3-item perceived susceptibility subscale for mammography screening to assess perceived susceptibility for delays starting PORT after HNSCC surgery. Items are rated on a 5-point Likert scale with higher scores indicating higher perceived susceptibility | Change from baseline to post-intervention (3 months) | 
| Change from Baseline in Illness Perception Questionnaire-Revised (IPQ-R) Consequences Subscale Score (HNSCC Modification) | An easily modifiable measure of disease-specific perceived severity.The IPQ-R is a validated assessment of a patient's self-representation of the health consequences of their illness. It is scored using a 5-point Likert scale with higher scores indicate higher perceived severity | Change from baseline to post-intervention (3 months) | 
| Change from Baseline in Perceived Barriers Scale | A self-report measure of the presence/absence of pre-specified barriers to cancer care (yes/no). The questionnaire has been used extensively to assess perceived barriers in prior PN studies | Change from baseline to post-intervention (3 months) | 
| Change from Baseline in Communication & Attitudinal Self-Efficacy Scale (CASE)-Cancer Score | A validated, psychometrically sound 12-item scale that addresses three domains of self-efficacy in cancer care (understanding and participating in care, maintaining a positive attitude, and seeking and obtaining information). The CASE-Cancer scale has been used extensively in PN studies to measure perceived self-efficacy. Responses are on a 4-point Likert scale with higher scores indicating higher levels of self-efficacy | Change from baseline to post-intervention (3 months) |