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

Locally Advanced Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05892354
• Other study ID #: FirstGuangxiMu3
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 10, 2023
• Est. completion date: February 1, 2026

Study information

• Verified date: May 2023
• Source: First Affiliated Hospital of Guangxi Medical University
• Contact: Min Kang, Ph.D
• Phone: 86-771-5356509
• Email: km1019[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 190
• Est. completion date: February 1, 2026
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;

2. Age 18-70 years old, male or non-pregnant women;

3. Pathologically confirmed non-keratinizing carcinoma of the nasopharynx (differentiated or undifferentiated,WHO type II or III);

4. Newly diagnosed stage III-IVa (8th AJCC/UICC stage) NPC patients;

5. 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:

1. History of investigational Oral Impact®/ENSURE® use within the month prior to enrollment;

2. Known allergy or intolerance to any component of investigational Oral Impact®/ENSURE® or related chemotherapy drugs;

3. Poor glycemic control in patients with diabetes;

4. Patients with autoimmune diseases;

5. Patients with active infections;

6. Patients who have received radiation therapy or other anti-tumor treatments in the past;

7. Patients with a history of other malignant tumors;

8. Presence of oral mucositis at baseline;

9. Malnutrition at baseline;

10. Patients who cannot eat the required amount of food at baseline and require parenteral or enteral nutrition;

11. Inability to eat soft solid foods at baseline;

12. History of human immunodeficiency virus (HIV) or active hepatitis B/C virus infection;

13. Participation in other intervention clinical studies within one month;

14. 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.

Related Conditions & MeSH terms

• Carcinoma
• Locally Advanced Nasopharyngeal Carcinoma
• Mucositis
• Nasopharyngeal Carcinoma
• Stomatitis

Intervention

Dietary Supplement:
• Enteral immunonutrition
Enteral immunonutrition (Oral Impact®, Nestle), 250ml/ bottle, 2 bottles per day, from 5 days before radiotherapy to the end of radiotherapy.
• Standard enteral nutrition
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).

Locations

Country	Name	City	State
n/a

Sponsors (19)

Lead Sponsor

Collaborator

First Affiliated Hospital of Guangxi Medical University

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Fujian Cancer Hospital, Fujian Provincial Hospital, Guangdong Provincial People's Hospital, Guilin Medical University, China, Haikou People's Hospital, Huizhou Municipal Central Hospital, Liuzhou Workers Hospital, Qingdao Central Hospital, Red Cross Hospital of Yulin City, Second Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Nanchang University, The Second Affiliated Hospital of Hainan Medical University, Wuzhou Red Cross Hospital, Zhejiang Cancer Hospital, Zhejiang Provincial People's Hospital, Zhejiang Provincial Tongde Hospital

References & Publications (10)

Boisselier P, Kaminsky MC, Thezenas S, Gallocher O, Lavau-Denes S, Garcia-Ramirez M, Alfonsi M, Cupissol D, de Forges H, Janiszewski C, Geoffrois L, Sire C, Senesse P; Head and Neck Oncology and Radiotherapy Group (GORTEC). A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Am J Clin Nutr. 2020 Dec 10;112(6):1523-1531. doi: 10.1093/ajcn/nqaa227. — View Citation

Dechaphunkul T, Arundon T, Raungkhajon P, Jiratrachu R, Geater SL, Dechaphunkul A. Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study. Clin Nutr. 2022 Feb;41(2):433-440. doi: 10.1016/j.clnu.2021.12.035. Epub 2021 Dec 28. — View Citation

Kabarriti R, Bontempo A, Romano M, McGovern KP, Asaro A, Viswanathan S, Kalnicki S, Garg MK. The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy. Support Care Cancer. 2018 Sep;26(9):3307-3313. doi: 10.1007/s00520-018-4198-x. Epub 2018 Apr 18. — View Citation

Liang L, Liu Z, Zhu H, Wang H, Wei Y, Ning X, Shi Z, Jiang L, Lin Z, Yan H, Wang R, Hu K. Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: A multicenter, open-label, randomized controlled trial. Cancer. 2022 Apr 1;128(7):1467-1474. doi: 10.1002/cncr.34074. Epub 2021 Dec 15. — View Citation

Miyata H, Yano M, Yasuda T, Yamasaki M, Murakami K, Makino T, Nishiki K, Sugimura K, Motoori M, Shiraishi O, Mori M, Doki Y. Randomized study of the clinical effects of omega-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Nutrition. 2017 Jan;33:204-210. doi: 10.1016/j.nut.2016.07.004. Epub 2016 Jul 25. — View Citation

Moslemi D, Nokhandani AM, Otaghsaraei MT, Moghadamnia Y, Kazemi S, Moghadamnia AA. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature. Radiother Oncol. 2016 Jul;120(1):13-20. doi: 10.1016/j.radonc.2016.04.001. Epub 2016 Apr 21. — View Citation

Shu Z, Zeng Z, Yu B, Huang S, Hua Y, Jin T, Tao C, Wang L, Cao C, Xu Z, Jin Q, Jiang F, Feng X, Piao Y, Huang J, Chen J, Shen W, Chen X, Wu H, Wang X, Qiu R, Lu L, Chen Y. Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study. Front Oncol. 2020 Nov 6;10:594687. doi: 10.3389/fonc.2020.594687. eCollection 2020. — View Citation

Talvas J, Garrait G, Goncalves-Mendes N, Rouanet J, Vergnaud-Gauduchon J, Kwiatkowski F, Bachmann P, Bouteloup C, Bienvenu J, Vasson MP. Immunonutrition stimulates immune functions and antioxidant defense capacities of leukocytes in radiochemotherapy-treated head & neck and esophageal cancer patients: A double-blind randomized clinical trial. Clin Nutr. 2015 Oct;34(5):810-7. doi: 10.1016/j.clnu.2014.12.002. Epub 2014 Dec 9. — View Citation

Xia C, Jiang C, Li W, Wei J, Hong H, Li J, Feng L, Wei H, Xin H, Chen T. A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma. Front Immunol. 2021 Mar 24;12:618150. doi: 10.3389/fimmu.2021.618150. eCollection 2021. — View Citation

Zheng Z, Zhao X, Zhao Q, Zhang Y, Liu S, Liu Z, Meng L, Xin Y, Jiang X. The Effects of Early Nutritional Intervention on Oral Mucositis and Nutritional Status of Patients With Head and Neck Cancer Treated With Radiotherapy. Front Oncol. 2021 Feb 1;10:595632. doi: 10.3389/fonc.2020.595632. eCollection 2020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of severe oral mucositis	Incidence of grade 3-4 oral mucositis	7 weeks
Secondary	The latency period of severe oral mucositis	Total duration from the start of radiotherapy to the severe oral mucositis	7 weeks
Secondary	The duration period of severe oral mucositis	The number of days of severe oral mucositis during the oral mucositis observation period	7 weeks
Secondary	Assessment of immune state	T-lymphocyte subsets	4 months
Secondary	Serum hypersensitive C-reactive protein (hsCRP) level	Change in high sensitivity C-reactive protein from baseline to end of radiotherapy	4 months
Secondary	Serum Interleukin-6 (IL-6) level	Change in serum level of Interleukin-6 from baseline to end of radiotherapy	4 months
Secondary	Hemoglobin level	Change in hemoglobin level from baseline to end of radiotherapy	4 months
Secondary	Serum albumin level	Change in hemoglobin level from baseline to end of radiotherapy	4 months
Secondary	Serum Pre-Albumin level	Change in hemoglobin level from baseline to end of radiotherapy	4 months
Secondary	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
Secondary	Nutrition status	Change in nutritional status determined by the Patient-Generated Subjective Global Assessment (PG-SGA) from baseline to end of radiotherapy	4 months
Secondary	Physical functional status	Changes in handgrip strength from baseline to end of radiotherapy	4 months
Secondary	overall survival rate (OS)	compare OS between two groups	at 2 years after randomisation
Secondary	progression-free survival rate (PFS)	compare PFS between two groups	at 2 years after randomisation
Secondary	Locoregional recurrence free survival rate (LRRFS)	compare LRRFS between two groups	at 2 years after randomisation
Secondary	Distance metastasis-free survival rate (DMFS)	compare DMFS between two groups	at 2 years after randomisation
Secondary	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
Secondary	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
Secondary	Number of participants with adverse events	Analysis of acute and late adverse events (AEs) are evaluated.	up to 2 years after randomisation