This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker nimotuzumab versus radiotherapy plus cisplatin(CCRT) for nasopharyngeal carcinoma (NPC) patients with favorable response to induction chemotheray(IC), determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT and may provide new evidence for individualized comprehensive treatment of locoregionally advanced NPC.
Currently, NCCN (National Comprehensive Cancer Network) guidelines recommend induction chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for locally advanced nasopharyngeal carcinoma (stage II-IVa). However, although induction chemotherapy combined with cisplatin based concurrent radiotherapy (CCRT) can significantly improve the survival of patients, the side effects during radiotherapy are more serious. Previous studies have demonstrated that with a cut-off point of 1500 copies/mL, NPC patients could be segregated into a low-risk subgroup and a high-risk subgroup. Besides, our previous results showed that patients with plasma Epstein-Barr virus (EBV) DNA= 0 copy/mL and complete response/partial response (CR/PR) after induction chemotherapy had a significantly lower risk of disease progression than patients with plasma EBV DNA\>0 copy/mL and stable disease /progressive disease (SD/PD),according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these low-risk and chemotheray sensitive patients, it can be considered to reduce the current standard treatment intensity without affecting the survival rate of patients, which reduces the side effects of patients and improve the their life qualities. Epidermal growth factor (EGFR) is an important therapeutic target for nasopharyngeal carcinoma. A retrospective study suggested that there was no significant difference in the 3-year overall survival between NPC patients who received nimotuzumab / cetuximab plus radiotherapy and those who received standard CCRT. Besides, in terms of hepatorenal toxicity, anti-EGFR drugs showed better safety compared with traditional cisplatin chemotherapy. Up to now, randomized clinical trial about the application of nimotuzumab after IC is still limited. This is a phase III randomized clinical trial of definitive radiotherapy plus EGFR blocker nimotuzumab versus radiotherapy plus cisplatin for NPC patients with favorable response after IC, determining whether radiotherapy combined with nimotuzumab was non-inferior to CCRT after IC and may provide new evidence for individualized comprehensive treatment of locoregionally advanced NPC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
381
Nimotuzumab (200mg, once a week during radiotherapy, a total of 7 weeks)
concurrent cisplatin (100mg/m2, every three weeks,D1,D22,D43 of intensity modulated radiotherapy )
Sun Yat-sen Universitty Cancer Center
Guangzhou, Guangdong, China
Progression-Free Survival (PFS)
Defined from date of randomization to date of first documentation of progression or death due to any cause
Time frame: 2 years
Overall Survival (OS)
Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.
Time frame: 2 years
Locoregional Relapse-Free Survival (LRFS)
Defined from date of randomization to date of first documentation of locoregional relapse or the date of death from any cause or until the date of the last follow-up visit
Time frame: 2 years
Distant Metastasis-Free Survival (DMFS)
Defined from date of randomization to date of first documentation of distant metastases or the date of death from any cause or until the date of the last follow-up visit
Time frame: 2 years
Objective Response Rate (ORR)
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)
Time frame: Three months after the completion of the CCRT with or without Nimotuzumab treatment
Incidence rate of adverse events (AEs)
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.
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Time frame: 2 years
Evaluate EGFR expression level and EGFR Gene Copy Number as a predictive marker for survival outcomes
Pre-treatment EGFR expression level and EGFR Gene Copy Number is evaluated by means of immunohistochemical testing and fluorescent in situ hybridization (FISH), respectively.
Time frame: 2 years
Change of QoL
QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy
Time frame: 1 years
Change of EORTC quality of life questionnaire(QLQ) Head and Neck score
QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H\&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.All of the scores mentioned above were assessed at the below time point:before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy
Time frame: 1 years
Plasma EBV DNA copy number
Plasma EBV DNA copy number in both arms was assessed by Quantitative real time polymerase chain reaction(qRT-PCR) at pretreatment, after two cycle induction chemotherapy, during CCRT and follow up time . The predictive value of plasma EBV DNA copy number was assessed by survival analysis.
Time frame: 2 years