Effect of Immunonutrients on Oral Mucositis in Nasopharyngeal Carcinoma Patients After Chemoradiotherapy

Study Overview
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Brief Summary
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The purpose of this study was to investigate the role of immunonutrion compared with standard nutrition in reducing oral mucositis in patients with locally advanced nasopharyngeal carcinoma.

Detailed Description
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Oral mucositis is the most common adverse reaction in patients with nasopharyngeal carcinoma receiving chemoradiotherapy, of which 40-50% of patients are severe (grade 3-4). Oral mucositis usually results in pain, dysphagia, reduced feeding, and malnutrition. Severe malnutrition in turn increases the risk of severe oral mucositis. Persistent severe oral mucositis will lead to delay and interruption of treatment, impairing patients'quality of life and prognosis. It's reported that nutritional intervention can not only reduce the risk and severity of oral mucositis and improve the nutritional status of patients with head and neck tumors, but also improve patients' tolerance to radiotherapy, quality of life, and prognosis. Immunonutrition refers to the addition of high content of immune nutrients on the basis of sufficient calories, which not only ensures the supply of nutrition, but also takes into account the effects of anti-inflammation, regulating immunity, improving treatment tolerance, improving prognosis and so on. It has been reported that, comparing with standard enteral nutrition, the incidence of severe oral mucositis and esophagitis in patients with head and neck tumors treated with immunonutrition was lower, suffering less weight loss, and the antitumor immune response was enhanced. The 3-year OS and PFS were significantly improved in patients with good compliance. It remains to be seen whether or not NPC patients receiving chemoradiotherapy can be benifit from immunonutritional therapy. Therefore, we conducted a prospective, multi-center, randomized controlled clinical study in patients with nasopharyngeal carcinoma who received radiotherapy and chemotherapy without metastases, to further improve the quality of life and prognosis of patients with nasopharyngeal carcinoma.

Official Title
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Efficacy of Immunonutrients in Reducing Oral Mucositis in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Prospective, Multicenter, Randomized Controlled Clinical Trial

Conditions
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Locally Advanced Nasopharyngeal Carcinoma

Intervention / Treatment
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* Dietary Supplement: Enteral immunonutrition
* Dietary Supplement: Standard enteral nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Age 18-70 years old, male or non-pregnant women; Pathologically confirmed non-keratinizing carcinoma of the nasopharynx (differentiated or undifferentiated,WHO type II or III); Newly diagnosed stage III-IVa (8th AJCC/UICC stage) NPC patients; The levels of major organ function meet the following criteria: (1)Hematology: WBC ≥ 3.0 × 10^9/L, ANC ≥ 1.5 × 10^9/L, PLT ≥ 100 × 10^9/L, HGB ≥ 90 g/L; (2) Liver function: ALT, AST≤2.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN; (3) Renal function: BUN and CRE ≤ 1.5 × ULN or an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min (calculated using the Cockcroft-Gault equation); (4) Adequate coagulation function: defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the ULN; (5) Normal levels of cardiac enzymes; 6. The patient has signed informed consent forms and is able to comply with the study's planned visits, treatment plans, and laboratory tests. Exclusion Criteria: History of investigational Oral Impact®/ENSURE® use within the month prior to enrollment; Known allergy or intolerance to any component of investigational Oral Impact®/ENSURE® or related chemotherapy drugs; Poor glycemic control in patients with diabetes; Patients with autoimmune diseases; Patients with active infections; Patients who have received radiation therapy or other anti-tumor treatments in the past; Patients with a history of other malignant tumors; Presence of oral mucositis at baseline; Malnutrition at baseline; Patients who cannot eat the required amount of food at baseline and require parenteral or enteral nutrition; Inability to eat soft solid foods at baseline; History of human immunodeficiency virus (HIV) or active hepatitis B/C virus infection; Participation in other intervention clinical studies within one month; Subjects deemed by the investigator to have other factors that may force them to terminate the study, such as having other serious illnesses (including mental illnesses) that require concomitant treatment, significantly abnormal laboratory test results, or family or social factors that may affect subject safety or data collection.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunonutrition Group<br>Induction chemotherapy (IC) + Concurrent chemoradiotherapy (CCRT) and enteral immunonutrition Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2-3 cycles before radiotherapy and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin (100mg/m² d1) every 3 weeks for 2-3 cycles. Patients receive enteral immunonutrition, Oral Impact®, Nestle, 250ml/ bottle, 2 bottles per day, from 5 days before radiotherapy to the end of radiotherapy. | Dietary Supplement: Enteral immunonutrition<br>* Enteral immunonutrition (Oral Impact®, Nestle), 250ml/ bottle, 2 bottles per day, from 5 days before radiotherapy to the end of radiotherapy.<br>|
| Active Comparator: Control Group<br>Induction chemotherapy+Concurrent chemoradiotherapy and standard enteral nutrition Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2-3 cycles before radiotherapy and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin(100mg/m² d1) every 3 weeks for 2-3 cycles. Patients receive isocaloric standard enteral nutrition formula (ENSURE®), 250 mL per administration, 3 times per day, from 5 days before radiotherapy to the end of radiotherapy. Preparation of the 250 mL dose involves adding 200 mL of potable water to a cup and slowly stirring in 52.7 g of ENSURE powder (approximately 6 scoops). | Dietary Supplement: Standard enteral nutrition<br>* Isocaloric standard enteral nutrition formula (ENSURE®)， 250 mL per administration, 3 times per day. Preparation of the 250 mL dose involves adding 200 mL of potable water to a cup and slowly stirring in 52.7 g of ENSURE powder (approximately 6 scoops).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of severe oral mucositis | Incidence of grade 3-4 oral mucositis | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The latency period of severe oral mucositis | Total duration from the start of radiotherapy to the severe oral mucositis | 7 weeks | 
| The duration period of severe oral mucositis | The number of days of severe oral mucositis during the oral mucositis observation period | 7 weeks | 
| Assessment of immune state | T-lymphocyte subsets | 4 months | 
| Serum hypersensitive C-reactive protein (hsCRP) level | Change in high sensitivity C-reactive protein from baseline to end of radiotherapy | 4 months | 
| Serum Interleukin-6 (IL-6) level | Change in serum level of Interleukin-6 from baseline to end of radiotherapy | 4 months | 
| Hemoglobin level | Change in hemoglobin level from baseline to end of radiotherapy | 4 months | 
| Serum albumin level | Change in hemoglobin level from baseline to end of radiotherapy | 4 months | 
| Serum Pre-Albumin level | Change in hemoglobin level from baseline to end of radiotherapy | 4 months | 
| Nutritional risk | Change in nutritional risk determined by the by the nutrition risk screening-2002 (NRS-2002) from baseline to end of radiotherapy | 4 months | 
| Nutrition status | Change in nutritional status determined by the Patient-Generated Subjective Global Assessment (PG-SGA) from baseline to end of radiotherapy | 4 months | 
| Physical functional status | Changes in handgrip strength from baseline to end of radiotherapy | 4 months | 
| overall survival rate (OS) | compare OS between two groups | at 2 years after randomisation | 
| progression-free survival rate (PFS) | compare PFS between two groups | at 2 years after randomisation | 
| Locoregional recurrence free survival rate (LRRFS) | compare LRRFS between two groups | at 2 years after randomisation | 
| Distance metastasis-free survival rate (DMFS) | compare DMFS between two groups | at 2 years after randomisation | 
| Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire | EORTC QLQ-C30 is a specific quality of life assessment scale based on EORTC QLQ-C 30, with 35 items. All of the scales and single-item measures range from 0 to 100. A EORTC QLQ-C30 is a specific quality of life assessment scale, with 30 items. All of the scales and single-item measures range from 0 to 100. More global and functional scales is better. less symptom scales is better. | 4 months | 
| Quality of life (QoL) assessed by the EORTC-QLQ-H&N35 Questionnaire | EORTC QLQ-H&N35 is a specific quality of life assessment scale based on EORTC QLQ-C 30, with 35 items. All of the scales and single-item measures range from 0 to 100. High scores represent increased (worse) symptoms. | 4 months | 
| Number of participants with adverse events | Analysis of acute and late adverse events (AEs) are evaluated. | up to 2 years after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunonutrition, Nasopharyngeal Carcinoma, Chemoradiotherapy, Oral Mucositis