Early Enteral Nutritional Supplementation on Patients With Oral and Oropharyngeal Cancer Undergoing Radio(Chemo)Therapy After Surgical

Study Overview
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Brief Summary
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The target population in the present study is Chinese patients with oral and oropharyngeal cancer who plan to receive radio(chemo)therapy after surgical resection in the outpatient department. Investigators hypothesize that early enteral nutrition intervention, which is initiated 2 weeks before the start of postoperative radio(chemo)therapy treatment and added on demand during radiotherapy, will improve patients' nutritional status, tolerability to the radio(chemo)therapy, quality of life, and other clinical outcomes compared to commencement of oral nutritional supplements during the course of irradiation treatment. There are two cohorts in this trial, cohort 1 included patients with oral nutritional supplements and cohort 2 included patients with tube feeding (nasogastric tube or percutaneous endoscopic gastrostomy).

Detailed Description
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This clinical trial will be conducted in a single-center, prospective, and randomized manner. In this protocol, the standard radio(chemo)therapy duration is 6-7 weeks. Early enteral nutrition intervention (EEN) refers to starting enteral nutrition intervention 2 weeks before post-operative radio(chemo)therapy begins and stopping this intervention when post-operative radio(chemo)therapy completes. Standard enteral nutrition intervention (SEN) refers to starting of enteral nutrition intervention on demand during (chemo)radiotherapy. Nutritional supplementation was given either through the oral route (Cohort 1) or tube feeding (nasogastric tube or percutaneous endoscopic gastrostomy, cohort 2). Dietitians will design meal plans for both groups of subjects so that their normal diets will provide 25-30 kcal/d/kg body weight in addition to nutritional supplements.

Official Title
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A Prospective, Randomized, Clinical Study to Evaluate the Effects of Early Enteral Nutritional Supplementation on Clinical Outcomes in Patients With Oral and Oropharyngeal Cancer Undergoing Radio(Chemo)Therapy After Surgical Resection

Conditions
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Malnutrition

Intervention / Treatment
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* Dietary Supplement: Early nutritional intervention


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subject is male or female, between 18 and 70 years old; Subject has clinical or radiological diagnosis of oral cancer (stage III and stage IV), had surgical resection 3 or 4 weeks prior to radio (chemo)therapy, and plans to receive radio (chemo)therapy treatment; Subject has Karnofsky Performance Score (KPS) ≥ 60 and an expected life expectancy ≥ 6 months; Subject is willing to comply with the study protocol, able and willing to consume study product according to the protocol; Subject has voluntarily signed and dated the informed consent form (ICF), approved by an Institutional Review Board (IRB) / Independent Ethics Committee (IEC) prior to any participation in the study Exclusion criteria Except for oral cancer and oropharyngeal cancer, subject has malignant tumors or serious infectious diseases, such as tuberculosis activity, respiratory system, cardiovascular system, urinary system diseases, systemic edema and ascites caused by diseases, etc., cannot participant in study in the opinion of study physician. Subject has dysfunction of liver, kidney or gallbladder, cannot participant in study in the opinion of study physician. Subject has gastrointestinal diseases to cannot tolerate enteral nutrition (such as intestinal bleeding, intestinal obstruction, severe digestive malabsorption, severe nausea and vomiting and diarrhea) that preclude his or her participation in the opinion of study physician; Subject has diabetes Subject has known history of allergy or intolerance to any ingredient in the investigational product; Female subjects are pregnant or plan to get pregnant within a year or are postpartum and non-lactating; Subject has mental illness, cannot understand ICF, unwilling to provide informed consent. Subject has amputation or implanted electronic devices or metal, it may be inappropriate to use BIA to measure body composition Subject is currently or has participated in any clinical trial 2 months prior to enrollment. Subject plans to take nutritional supplements and/or traditional Chinese medicine regularly during study in the opinion of study physician. Multi-vitamin and multi-mineral supplements are exception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cohort 1: nutritional supplements are given through oral route Cohort 2: nutritional supplements are given by tube feeding
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1-intervention<br>Oral supplements are given through oral route 2 weeks before radiotherapy. | Dietary Supplement: Early nutritional intervention<br>* Early nutritional intervention (Ensure) was given two weeks before radiotherapy. Ensure 3 times per day, Mixing 55.8 g or 6 spoons of Ensure with 190 mL of warm water.<br>|
| Active Comparator: Cohort 1-Control<br>Oral supplements are given through oral route on demand during radiotherapy. | Dietary Supplement: Early nutritional intervention<br>* Early nutritional intervention (Ensure) was given two weeks before radiotherapy. Ensure 3 times per day, Mixing 55.8 g or 6 spoons of Ensure with 190 mL of warm water.<br>|
| Experimental: Cohort 2- Intervention<br>Oral supplements are given by tube feeding 2 weeks before radiotherapy. | Dietary Supplement: Early nutritional intervention<br>* Early nutritional intervention (Ensure) was given two weeks before radiotherapy. Ensure 3 times per day, Mixing 55.8 g or 6 spoons of Ensure with 190 mL of warm water.<br>|
| Active Comparator: Cohort 2- Control<br>Oral supplements are given by tube feeding on demand during radiotherapy. | Dietary Supplement: Early nutritional intervention<br>* Early nutritional intervention (Ensure) was given two weeks before radiotherapy. Ensure 3 times per day, Mixing 55.8 g or 6 spoons of Ensure with 190 mL of warm water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | changes of body weight from baseline to Final Visit/Exit. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Changes of body weight from baseline to V2, V3 and V4 | 2weeks,5 weeks, 8 weeks | 
| Body Mass Index | Body Mass Index variables at baseline to V2, V3,V4 and Final Visit/Exit | 10 weeks | 
| Calf circumference by measure | Calf circumference variables at baseline to V3 and Final Visit/Exit | 5weeks, 10 weeks | 
| Lean mass measured by Bioelectrical impedance analysis (BIA) | Lean mass variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Fat mass measured by Bioelectrical impedance analysis (BIA) | Fat mass variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Patient-Generated Subjective Global Assessment/PG-SGA scores | PG-SGA scores, an assessment tool for nutritional status at baseline, V3 and Final Visit/Exit. The Scored PG-SGA includes the four patient-generated historical components (Weight History, Food Intake, Symptoms and Activities and Function), the professional part (Diagnosis, Age, Metabolic stress, and Physical Exam), the Global Assessment (A = well nourished, B = moderately malnourished or suspected malnutrition, C = severely malnourished), the total numerical score, and nutritional triage Recommendations (0-1=No intervention required, 2-3 Education and lab values as appropriate, 4-8 Required intervention, >=9 Indicates a critical need for improved and/or nutrient intervention). Subtotal 4 historical components: scoring 0-30+ Weight history and Symptoms scores are additive Food intake and Activities and Function, the highest point score, Professional component: Criteria for condition, scoring 0-6 Metabolic Stress, scoring 0-3 Physical components, scoring 0-3 | 5weeks 10 weeks | 
| Dietary adherence and intake assessment | Dietary adherence and intake assessment will be conducted by dietitians at V2, V3, V4 and Final Visit/Exit. Dietary adherence will be determined through comparing subjects' meal plans and actual consumptions as reflected by food diaries. | 2weeks,5 weeks, 8 weeks, 10 weeks | 
| Prealbumin by drawing blood | Prealbumin variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Albumin by drawing blood | Albumin variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Hemoglobin by drawing blood | Hemoglobin variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| White blood cell by drawing blood | White blood cell variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Peripheral blood lymphocyte by drawing blood | Peripheral blood lymphocyte variables at baseline, V3 and Final Visit/Exit | 5weeks 10 weeks | 
| Tolerability to radio(chemo)therapy assessment on treatment status | Treatment status (e.g., treatment course and doses completed as planned or changed) since last visit at V3, V4 and Final Visit/Exit | 5 weeks, 8 weeks, 10 weeks | 
| Tolerability to radio(chemo)therapy assessment on treatment change due to side effects | Number of days when treatment is suspended due to side effects since last visit at V3, V4 and Final Visit/Exit | 5 weeks, 8 weeks, 10 weeks | 
| Tolerability to radio(chemo)therapy assessment on complications | Incidence of radio(chemo)therapy-related complications such as oral mucositis, pneumonia, and shingles since last visit at V3, V4 and Final Visit/Exit | 5 weeks, 8 weeks, 10 weeks | 
| Tolerability to radio(chemo)therapy assessment on staying in hospital due to complications | Number of days when patients stay in hospital for treatment of radio(chemo)therapy-related complications since last visit at V3, V4 and Final Visit/Exit (if applicable) | 5 weeks, 8 weeks, 10 weeks | 
| Quality of life assessed by Quality of Life Questionnaire-Core 36 of European Organization for Research on Treatment of Cancer/EORTC Quality of Life QLQ-C30 questionnaire | Subjective assessment of physical activity, mood, fatigue and eating status by EORTC Quality of Life QLQ-C30 questionnaire at baseline, V3, V4 and Final Visit/Exit | 5 weeks, 8 weeks, 10 weeks | 
| Quality of life assessed by Quality of Life Questionnaire-Head and Neck 35 questionnaire of European Organization for Research on Treatment of Cancer/EORTC Quality of Life QLQ-H&N35 | Subjective assessment of physical activity, mood, fatigue and eating status by EORTC Quality of Life QLQ-H&N35 questionnaire at baseline, V3, V4 and Final | 5 weeks, 8 weeks, 10 weeks | 
| Health economics assessment on medications treatment due to complications | Costs for medications treated for radio(chemo)therapy-related complications during this study | 10 weeks | 
| Radio(chemo)therapy treatment effect | The variable is local tumor control probability assessed at baseline and Final Visit/Exit. Local tumor control probability is defined as the percentage of patients who do not have tumor recurrence in the total patients. | 10 weeks |