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

Primary Purpose

Locally Advanced Nasopharyngeal Carcinoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Enteral immunonutrition
Standard enteral nutrition
Sponsored by
First Affiliated Hospital of Guangxi Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Locally Advanced Nasopharyngeal Carcinoma focused on measuring Immunonutrition, Nasopharyngeal Carcinoma, Chemoradiotherapy, Oral Mucositis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Immunonutrition Group

    Control Group

    Arm Description

    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.

    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).

    Outcomes

    Primary Outcome Measures

    The incidence of severe oral mucositis
    Incidence of grade 3-4 oral mucositis

    Secondary Outcome Measures

    The latency period of severe oral mucositis
    Total duration from the start of radiotherapy to the severe oral mucositis
    The duration period of severe oral mucositis
    The number of days of severe oral mucositis during the oral mucositis observation period
    Assessment of immune state
    T-lymphocyte subsets
    Serum hypersensitive C-reactive protein (hsCRP) level
    Change in high sensitivity C-reactive protein from baseline to end of radiotherapy
    Serum Interleukin-6 (IL-6) level
    Change in serum level of Interleukin-6 from baseline to end of radiotherapy
    Hemoglobin level
    Change in hemoglobin level from baseline to end of radiotherapy
    Serum albumin level
    Change in hemoglobin level from baseline to end of radiotherapy
    Serum Pre-Albumin level
    Change in hemoglobin level from baseline to end of radiotherapy
    Nutritional risk
    Change in nutritional risk determined by the by the nutrition risk screening-2002 (NRS-2002) from baseline to end of radiotherapy
    Nutrition status
    Change in nutritional status determined by the Patient-Generated Subjective Global Assessment (PG-SGA) from baseline to end of radiotherapy
    Physical functional status
    Changes in handgrip strength from baseline to end of radiotherapy
    overall survival rate (OS)
    compare OS between two groups
    progression-free survival rate (PFS)
    compare PFS between two groups
    Locoregional recurrence free survival rate (LRRFS)
    compare LRRFS between two groups
    Distance metastasis-free survival rate (DMFS)
    compare DMFS between two groups
    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.
    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.
    Number of participants with adverse events
    Analysis of acute and late adverse events (AEs) are evaluated.

    Full Information

    First Posted
    April 24, 2023
    Last Updated
    May 29, 2023
    Sponsor
    First Affiliated Hospital of Guangxi Medical University
    Collaborators
    Guangdong Provincial People's Hospital, Zhejiang Cancer Hospital, Zhejiang Provincial People's Hospital, Fujian Cancer Hospital, Fujian Provincial Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, The First Affiliated Hospital of Nanchang University, Second Affiliated Hospital of Nanchang University, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Qingdao Central Hospital, Huizhou Municipal Central Hospital, Haikou People's Hospital, The Second Affiliated Hospital of Hainan Medical University, Zhejiang Provincial Tongde Hospital, Guilin Medical University, China, Liuzhou Workers Hospital, Wuzhou Red Cross Hospital, Red Cross Hospital of Yulin City
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05892354
    Brief Title
    Effect of Immunonutrients on Oral Mucositis in Nasopharyngeal Carcinoma Patients After Chemoradiotherapy
    Official Title
    Efficacy of Immunonutrients in Reducing Oral Mucositis in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Prospective, Multicenter, Randomized Controlled Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 10, 2023 (Anticipated)
    Primary Completion Date
    May 1, 2024 (Anticipated)
    Study Completion Date
    February 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    First Affiliated Hospital of Guangxi Medical University
    Collaborators
    Guangdong Provincial People's Hospital, Zhejiang Cancer Hospital, Zhejiang Provincial People's Hospital, Fujian Cancer Hospital, Fujian Provincial Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, The First Affiliated Hospital of Nanchang University, Second Affiliated Hospital of Nanchang University, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Qingdao Central Hospital, Huizhou Municipal Central Hospital, Haikou People's Hospital, The Second Affiliated Hospital of Hainan Medical University, Zhejiang Provincial Tongde Hospital, Guilin Medical University, China, Liuzhou Workers Hospital, Wuzhou Red Cross Hospital, Red Cross Hospital of Yulin City

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Locally Advanced Nasopharyngeal Carcinoma
    Keywords
    Immunonutrition, Nasopharyngeal Carcinoma, Chemoradiotherapy, Oral Mucositis

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    190 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Immunonutrition Group
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Control Group
    Arm Type
    Active Comparator
    Arm Description
    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).
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Enteral immunonutrition
    Intervention Description
    Enteral immunonutrition (Oral Impact®, Nestle), 250ml/ bottle, 2 bottles per day, from 5 days before radiotherapy to the end of radiotherapy.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Standard enteral nutrition
    Intervention Description
    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).
    Primary Outcome Measure Information:
    Title
    The incidence of severe oral mucositis
    Description
    Incidence of grade 3-4 oral mucositis
    Time Frame
    7 weeks
    Secondary Outcome Measure Information:
    Title
    The latency period of severe oral mucositis
    Description
    Total duration from the start of radiotherapy to the severe oral mucositis
    Time Frame
    7 weeks
    Title
    The duration period of severe oral mucositis
    Description
    The number of days of severe oral mucositis during the oral mucositis observation period
    Time Frame
    7 weeks
    Title
    Assessment of immune state
    Description
    T-lymphocyte subsets
    Time Frame
    4 months
    Title
    Serum hypersensitive C-reactive protein (hsCRP) level
    Description
    Change in high sensitivity C-reactive protein from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Serum Interleukin-6 (IL-6) level
    Description
    Change in serum level of Interleukin-6 from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Hemoglobin level
    Description
    Change in hemoglobin level from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Serum albumin level
    Description
    Change in hemoglobin level from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Serum Pre-Albumin level
    Description
    Change in hemoglobin level from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Nutritional risk
    Description
    Change in nutritional risk determined by the by the nutrition risk screening-2002 (NRS-2002) from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Nutrition status
    Description
    Change in nutritional status determined by the Patient-Generated Subjective Global Assessment (PG-SGA) from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    Physical functional status
    Description
    Changes in handgrip strength from baseline to end of radiotherapy
    Time Frame
    4 months
    Title
    overall survival rate (OS)
    Description
    compare OS between two groups
    Time Frame
    at 2 years after randomisation
    Title
    progression-free survival rate (PFS)
    Description
    compare PFS between two groups
    Time Frame
    at 2 years after randomisation
    Title
    Locoregional recurrence free survival rate (LRRFS)
    Description
    compare LRRFS between two groups
    Time Frame
    at 2 years after randomisation
    Title
    Distance metastasis-free survival rate (DMFS)
    Description
    compare DMFS between two groups
    Time Frame
    at 2 years after randomisation
    Title
    Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire
    Description
    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.
    Time Frame
    4 months
    Title
    Quality of life (QoL) assessed by the EORTC-QLQ-H&N35 Questionnaire
    Description
    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.
    Time Frame
    4 months
    Title
    Number of participants with adverse events
    Description
    Analysis of acute and late adverse events (AEs) are evaluated.
    Time Frame
    up to 2 years after randomisation

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Min Kang, Ph.D
    Phone
    86-771-5356509
    Email
    km1019@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Zhen Meng, Ph.D
    Phone
    86-771-5356509
    Email
    mengzhen0307@163.com

    12. IPD Sharing Statement

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

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