PRO-ACTIVE: Prophylactic Swallow Intervention for Patients Receiving Radiotherapy for Head and Neck Cancer

Study Overview
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Brief Summary
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Dysphagia (difficulty swallowing) is a common and potentially life-threatening toxicity of radiotherapy (RT) for patients with head and neck cancer (HNC). HNC survivors have a 20-24 percent lifetime risk of pneumonia after RT, which is associated with a 42 percent excess risk of death in survivorship. Moreover, dysphagia predisposes individuals to malnutrition, and at least half of HNC patients require feeding tubes during RT. Patients are commonly referred for swallowing therapy with a speech pathologist. Some patients receive early intervention, before a swallowing problem begins-PRO-ACTIVE therapy. Other patients are monitored and prescribed dysphagia interventions only if and when a swallowing problem occurs-RE-ACTIVE therapy. Thus, REACTIVE therapy aims to reverse an already impaired swallowing ability, whereas PRO-ACTIVE therapy aims to prevent or reduce severity of dysphagia. These two broad categories of therapy represent the most common types of intervention offered to HNC patients across North America. Although there is single-institution evidence to support each practice, it is yet unknown which is most effective. To address this gap, the primary aim of this international, multi-site 3-arm pragmatic randomized clinical trial is to compare the effectiveness of PRO-ACTIVE (high and low intensity) versus RE-ACTIVE swallowing therapy among 952 patients with HNC planning to undergo RT, using duration of feeding tube dependence after RT as the primary outcome. Our secondary aim proposes to compare the relative benefit or harm of these swallowing interventions on secondary outcomes considered relevant to our stakeholder partners.

Detailed Description
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Swallowing therapy is commonly provided as a behavioral treatment to lessen the risk or severity of dysphagia in head and neck cancer (HNC) patients; however, best practice is not established. This multi-site, international randomized clinical trial (RCT) will compare the effectiveness of PRO-ACTIVE (high and low intensity) versus RE-ACTIVE swallowing interventions in 952 HNC patients undergoing radiotherapy (RT). The 3 study arms represent alternate timing and intensity of swallowing therapy delivered by a speech language pathologist: 1) RE-ACTIVE, 2) PRO-ACTIVE EAT, and 3) PRO-ACTIVE EAT + EXERCISE. The primary aim of the PRO-ACTIVE trial is to compare the effectiveness of PRO-ACTIVE versus RE-ACTIVE swallowing interventions among patients with HNC planned to undergo RT. We hypothesize that the combined PRO-ACTIVE therapies are more effective than RE-ACTIVE therapy; and, if so, that more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to less intensive PRO-ACTIVE (EAT). Effectiveness will be measured based on reduced duration of feeding tube dependency as the primary endpoint, an outcome valued equally by patients, caregivers and clinicians. The secondary aim of the PRO-ACTIVE trial is to compare the relative benefit or harm of swallowing therapy arms on secondary outcomes including videofluoroscopic swallowing evaluations, functional status measures, health status measures, and patient-reported outcomes.

Official Title
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PRO-ACTIVE: Comparing The Effectiveness of Prophylactic Swallow Intervention for Patients Receiving Radiotherapy for Head and Neck Cancer

Conditions
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Dysphagia

Intervention / Treatment
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* Behavioral: RE-ACTIVE
* Behavioral: PRO-ACTIVE EAT
* Behavioral: PRO-ACTIVE EAT + EXERCISE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years of age diagnosed with head and neck malignancy; RT treatment planned for curative intent; Dispositioned to receive external beam radiotherapy dose ≥60 gray to bilateral fields at participating institution; Sufficient fluency in written English, French, Spanish or Simplified Chinese to be able to complete the study patient reported outcome questionnaires Exclusion Criteria: Distant metastasis at enrollment; or Prior or planned total laryngectomy; or Moderate/severe dysphagia at enrollment per baseline videofluoroscopy DIGEST grade ≥2 (as graded per central laboratory review) Previously seen by speech language pathologist for swallowing therapy for the current head and neck cancer Diagnosis of second primary non-head and neck cancers in the thorax or the central nervous system at enrollment Head and neck radiotherapy for thyroid or cutaneous/skin primary tumors, regardless of neck fields

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RE-ACTIVE<br>Reactive intervention started promptly if/when dysphagia is identified (RE-ACTIVE) | Behavioral: RE-ACTIVE<br>* Reactive intervention started promptly if/when dysphagia is identified<br>|
| Active Comparator: PRO-ACTIVE EAT<br>Early low intensity proactive intervention started before RT commences | Behavioral: PRO-ACTIVE EAT<br>* Early low intensity proactive intervention started before RT commences<br>|
| Active Comparator: PRO-ACTIVE EAT + EXERCISE<br>Early high intensity proactive intervention started before RT commences | Behavioral: PRO-ACTIVE EAT + EXERCISE<br>* Early high intensity proactive intervention started before RT commences<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of feeding tube dependence | Effectiveness will be measured based on duration of feeding tube dependency (count of days from end of radiotherapy to last feeding tube use within the 12-month study period) | Baseline - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The MD Anderson Dysphagia Inventory (MDADI) | Measurement of swallowing-related Quality of Life | Baseline, Week 6/7, 3 months, 12 months | 
| The MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) | Measurement of severity or burden of cancer-related symptoms and interference with daily functioning. | Baseline, Week 2, Week 4, Week 6/7, 3 months, 12 months | 
| Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) | Videofluoroscopy study score ranging from 0 to 5, where 4 is worst. | Baseline, 3 months, 12 months | 
| Pharyngeal Constriction Ratio (PCR) | Videofluoroscopy study score ranging from 0 to 1, where 1 is worst. | Baseline, 3 months, 12 months | 
| Penetration-Aspiration Scale (PAS) | Videofluoroscopy study score ranging from 1 to 8, where 8 is worst. | Baseline, 3 months, 12 months | 
| Peak esophageal opening | Videofluoroscopy study score ranging from 0 to infinity, where lower value is worse. | Baseline, 3 months, 12 months | 
| Performance Status Scale Head and Neck (PSS-HN) | Measurement of swallowing and speech performance | Baseline, Week 2, Week 4, Week 6/7, 3 months, 12 months | 
| Medical Outcome of Dysphagia (MOD) | Patient reported symptoms related to health consequences secondary to dysphagia, namely: malnutrition, aspiration pneumonia and mood changes such as depression and anxiety | Baseline, 3 months, 12 months | 
| Cancer Behavior Inventory (CBI-V3) | Measurement of self-efficacy strategies for coping with cancer | Baseline, 3 months, 12 months | 
| EQ-5D-5L | Measurement of generic quality of life | Baseline, 3 months, 12 months | 
| Medical History | Intake details, radiation therapy details, chemotherapy details, tumour status, surgery history, tracheotomy, feeding tube status, feeding tube dependence, concomitant therapies, and complication details. | Baseline, Week 6/7, 3 months, 12 months | 
| Pain Medications | All pain medications (including over-the-counter) taken in the past 48 hours | Baseline; Week 6/7, 3 Month, and 12 Months | 
| Mouth Opening/Trismus | Measurement of interincisal opening | Baseline; 3 Month and 12 Months | 
| Hospitalization/Emergency Department (ED) Presentation | Hospitalization/ED presentation at cancer hospital or any external institutions | Baseline, Week 6/7, 3 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dysphagia, swallowing disorder, speech pathology, swallowing therapy, head and neck cancer, radiotherapy, toxicity, supportive care