Efficacy of Ulinastatin for Reducing Radiation-Induced Oral Mucositis in Nasopharyngeal Carcinoma Patients

NCT ID: NCT03387774

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-30
• Study Completion Date: 2024-01-31

Brief Summary

This is a phase 3, open-label, multicenter, randomized controlled phase III clinical trial. The purpose of this study is to evaluate the efficacy of ulinastatin, a kind of protease inhibitor, in the treatment of radiation-induced acute oral mucositis in localregionally advanced nasopharyngeal carcinoma(NPC) patients treated with concurrent chemoradiotherapy(CCRT). To Explore a new and efficient way to reduce the incidence and severity of radiation-induced acute oral mucositis.

Detailed Description

Radiation-induced acute oral mucositis (RTOM) in Nasopharyngeal Carcinoma (NPC) patients treat with concurrent chemoradiotherapy (CCRT) is common. Currently, there is no effective treatment for RTOM. Ulinastatin, is a kind of natural anti-inflammatory substance. And this substance is insufficient when the body's inflammatory response is strongly. There are a series of studies have confirmed the efficacy and safety of ulinastatin in the treatment of body's inflammatory response. From the observation of our previous clinical practice, we found that ulinastatin can relieve the severity of RTOM. The present study is undertaken to evaluate the efficacy of ulinastatin in the treatment of RTOM in localregionally advanced NPC patients treated with CCRT.

Conditions

Oral Mucositis (Ulcerative) Due to Radiation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concurrent chemoradiotherapy and ulinastatin

Concurrent chemoradiotherapy (CCRT) and intravenous drip of ulinastatin, the details are as follows:

1. Intensity modulated radiation therapy combined with concurrent chemotherapy of cisplatin 100mg/m2 on day 1 and day 22 of RT;

2. Ulinastatin through intravenous drip at a dose of one hundred thousand units added to 100 ml of 0.9% normal saline, 3 times every radiation day, until the end of radiotherapy.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Patients in both arms received concurrent cisplatin chemotherapy:

100 mg/m² cisplatin given intravenously every 3 weeks on days 1, 22 concurrently with radiotherapy.

Intensity Modulated Radiation Therapy

Intervention Type: RADIATION

Patients in both arms received Intensity Modulated Radiation Therapy:

All target volumes were outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes were defined in accordance with the International Commission on Radiation Units and Measurements Reports 50 and 62. The prescribed dose was 68-72 Gy to PTVnx (Planning target volume of the primary tumor), 64-68 Gy to GTVnd (Gross tumor volume of the cervical lymph node), 60- 64Gy to PTVnd and PTV1 (Planning target volume 1), and 54-58 Gy to PTV2 (Planning target volume 2) in 30-32 fractions. The details of dose limits for organs at risk were based on the study 0225 from The Radiation Therapy Oncology Group (RTOG 0225).

Ulinastatin

Intervention Type: DRUG

Patients in the experimental group were received ulinastatin:

Ulinastatin (UTI): ulinastatin was intravenous drip at a dose of one hundred thousand units added to 100 ml of 0.9% normal saline every time, 3 times every radiation day, and until the end of radiotherapy.

Concurrent chemoradiotherapy

Concurrent chemoradiotherapy (CCRT) alone:

Intensity modulated radiation therapy combined with concurrent chemotherapy of cisplatin 100mg/m2 on day 1 and day 22 of RT.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Patients in both arms received concurrent cisplatin chemotherapy:

100 mg/m² cisplatin given intravenously every 3 weeks on days 1, 22 concurrently with radiotherapy.

Intensity Modulated Radiation Therapy

Intervention Type: RADIATION

Patients in both arms received Intensity Modulated Radiation Therapy:

All target volumes were outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes were defined in accordance with the International Commission on Radiation Units and Measurements Reports 50 and 62. The prescribed dose was 68-72 Gy to PTVnx (Planning target volume of the primary tumor), 64-68 Gy to GTVnd (Gross tumor volume of the cervical lymph node), 60- 64Gy to PTVnd and PTV1 (Planning target volume 1), and 54-58 Gy to PTV2 (Planning target volume 2) in 30-32 fractions. The details of dose limits for organs at risk were based on the study 0225 from The Radiation Therapy Oncology Group (RTOG 0225).

Interventions

Cisplatin

Patients in both arms received concurrent cisplatin chemotherapy:

100 mg/m² cisplatin given intravenously every 3 weeks on days 1, 22 concurrently with radiotherapy.

Intervention Type: DRUG

Intensity Modulated Radiation Therapy

Patients in both arms received Intensity Modulated Radiation Therapy:

All target volumes were outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes were defined in accordance with the International Commission on Radiation Units and Measurements Reports 50 and 62. The prescribed dose was 68-72 Gy to PTVnx (Planning target volume of the primary tumor), 64-68 Gy to GTVnd (Gross tumor volume of the cervical lymph node), 60- 64Gy to PTVnd and PTV1 (Planning target volume 1), and 54-58 Gy to PTV2 (Planning target volume 2) in 30-32 fractions. The details of dose limits for organs at risk were based on the study 0225 from The Radiation Therapy Oncology Group (RTOG 0225).

Intervention Type: RADIATION

Ulinastatin

Patients in the experimental group were received ulinastatin:

Ulinastatin (UTI): ulinastatin was intravenous drip at a dose of one hundred thousand units added to 100 ml of 0.9% normal saline every time, 3 times every radiation day, and until the end of radiotherapy.

Intervention Type: DRUG

Other Intervention Names

DDP; IMRT; UTI for injection

Eligibility Criteria

Inclusion Criteria

• Newly histologic diagnosis of nasopharyngeal carcinoma without distant metastasis
• Clinical stage III~IVa( UICC (Union International Against Cancer) /AJCC (American Joint Committee on Cancer) TNM staging system 8th edition)
• Karnofsky Performance Status Scale between 80-100
• WBC count ≥ 4×109/L，neutrophil differential count≥ 1.5×109/L,Hemoglobin ≥ 90g/L， platelet count ≥ 100×109/L
• ALT or AST ≤2.5×ULN,bilirubin ≤2.5×ULN,Serum creatinine ≤1.5×ULN or Serum creatinine clearance≥60ml/min
• Sign the informed consent.

Exclusion Criteria

• Angle of sexual squamous cell carcinomas and basal cell layout, squamous cell carcinomas
• Younger than 18 years old or older than 70 years old
• Pregnancy or lactation
• Severe cerebrovascular disease/canker/psychosis/uncontrolled diabetes
• Have suffered from other tumor or now suffering from other tumor
• Have suffered from oral diseases or salivary gland diseases or mow suffering from oral diseases or salivary gland diseases
• Refuse to give up smoking/drinking/betel chewing
• suffering from other active infection diseases and in need of treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

First People's Hospital of Foshan

OTHER

Sponsor Role: collaborator

Fifth Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Zhao Chong

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

zhao chong

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Related Links

http://www.sysucc.org.cn

Home Page of Cancer Center, Sun Yat-sen University

Other Identifiers

UTI-RTOM-NPC

Identifier Type: -

Identifier Source: org_study_id