4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation Versus Concurrent Chemoradiation Alone In Patients With Stage N2-3 Nasopharyngeal Carcinoma: A Phase 3 Multicenter Randomised Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 192
- 试验地点
- 4
- 主要终点
- 5-year distant-metastasis-free survival (5y-MFS)
研究概览
简要总结
The standard treatment strategy of locally advanced nasopharyngeal carcinoma (NPC) nowadays is concurrent chemoradiation (CCRT) based on intensity-modulated radiation therapy (IMRT). However, distant metastasis remains the major cause of treatment failure, especially in patients with T1-4N2-3M0 diseases (N2-3 NPC). The investigators inferred that it was more appropriate to consider N2-3 NPC as a systemic disease instead of a local disease. NACT of sufficient intensity such as 4 cycles might be effective enough for control of the pre-existing micrometastases. Therefore, the objective of this phase 3 multicenter randomized controlled trial is to make a comparison between NACT of 4 cycles plus CCRT based on IMRT and CCRT alone in N2-3 NPC on distant metastasis, survival and adverse reaction.
详细描述
The standard treatment strategy of locally advanced nasopharyngeal carcinoma (NPC) nowadays is concurrent chemoradiation (CCRT), which is based on intensity-modulated radiation therapy (IMRT) and achieves a satisfactory local-regional control and a 5-year overall survival (OS) of 83.0%. However, distant metastasis remains the major cause of treatment failure, especially in patients with T1-4N2-3M0 diseases (N2-3 NPC). The distant metastasis reaches 35-48% after CCRT alone.
To decrease distant metastasis of locally advanced NPC so as to improve survival, approaches on modifying timing of chemotherapy have been made to mainly 2 types: one was CCRT plus adjuvant chemotherapy (ACT), the other was neoadjuvant chemotherapy (NACT) plus CCRT. It was proved that CCRT plus ACT could not improve survival of locally advanced NPC further. Some clinical trials indicated that locally advanced NPC patients with 2-3 cycles of NACT plus CCRT had a better survival than those with CCRT alone though the roles of NACT remain controversial.
It is known that N stage is by far the most significant predicting factor of metastasis risk for NPC. N2-3 NPC was also proved to have a quite great risk of distant failure. 51.4% of distant metastases happened within 1 year after CCRT. The investigators inferred that subclinical micrometastases were already present before treatment starting. Hence, it was more appropriate to consider N2-3 NPC as a systemic disease instead of a local disease. NACT of sufficient intensity such as 4 cycles might be effective enough for control of the pre-existing micrometastases.
Therefore, this phase 3 multicenter randomized controlled trial is conducted to enroll 144 patients with N2-3 NPC. After stratification by N stage, the patients will be allocated into 2 treatment groups randomly at a ratio of 1:1 and applied with different treatment strategies to make a comparison between NACT of 4 cycles plus CCRT based on IMRT and CCRT alone in N2-3 NPC on distant metastasis, survival and adverse reaction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with pathological diagnosis of nasopharyngeal carcinoma
- •Union Internationale Contre le Cancer/American Joint Cancer Committee (UICC/AJCC) 2010 Stage T1-4 N2-3 M0 through magnetic resonance imaging of head and neck, whole-body bone scan and thoracoabdominal computed tomography
- •Male or female with age no older than 70 years old
- •Karnofsky Performance Scores ≥ 80
- •Expected survival ≥ 3 months
排除标准
- •Patients with distant metastasis before or during radiotherapy
- •Severe dysfunction of heart, lung, liver, kidney or hematopoietic system
- •Severe neurological, mental or endocrine diseases
- •History of other malignancies
- •Prior chemotherapy, radiotherapy or application of monoclonal antibodies
- •Patients participated in clinical trials of other drugs within last 3 months
- •Pregnant or lactating women
- •Those who are considered by the researchers unsuitable to participate
研究组 & 干预措施
CCRT group (Group A)
Patients who are allocated into in this group will be treated with concurrent chemoradiation (CCRT).
干预措施: Concurrent chemoradiation (CCRT) (Radiation)
NACT-CCRT group (Group B)
Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.
干预措施: Docetaxel (DOC) (Drug)
NACT-CCRT group (Group B)
Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.
干预措施: Cisplatin (DDP) (Drug)
NACT-CCRT group (Group B)
Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.
干预措施: Concurrent chemoradiation (CCRT) (Radiation)
结局指标
主要结局
5-year distant-metastasis-free survival (5y-MFS)
时间窗: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive without distant metastasis for a 5-year period of follow-up after the date of pathologic diagnosis
5-year overall survival (5y-OS)
时间窗: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive for a 5-year period of follow-up after the date of pathologic diagnosis
次要结局
- 5-year local-relapse-free survival (5y-RFS)(5 years after the date of pathologic diagnosis)
- Incidence of grade 3/4 adverse event(Once a week during therapy, up to 7 weeks (Group A) or 19 weeks (Group B))
- 5-year disease-free survival (5y-DFS)(5 years after the date of pathologic diagnosis)
研究者
Yuan-hong Gao
Deputy Director of Department of Radiation Oncology, Sun Yat-sen University Cancer Center
Sun Yat-sen University