This is an Open Label, Non-Inferiority, Multicenter, Randomized Phase 3 Trial aimed to investigate the impact of reduced-dose radiotherapy in combination with chemotherapy and immunotherapy on patients' prognosis and complication compared with conventional-dose radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive stage III NPC patients screened out according to the treatment response.
The goals of this clinical trial includes: ① To confirm whether LRRFS after reduced-dose radiotherapy in combination with chemotherapy and immunotherapy is non-inferior to LRRFS after conventional-dose radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive stage III NPC patients screened out according to the treatment response; ② To explore the impact of reduced-dose radiotherapy on 3-year OS, 3-year PFS, 3-year DMFS, 3-year LRFS and 3-year RRFS for treatment-sensitive stage III NPC patients screened out according to the treatment response; ③ To explore the impact of reduced-dose radiotherapy on radiotherapy complications and quality of life; ④ To explore the interaction between different clinical factors and the impact of reduced-dose radiotherapy on the prognosis of patients; ⑤ To explore the biomarkers of sensitivity to chemotherapy and radiotherapy for patients with nasopharyngeal carcinoma and the underlying mechanism. For these purposes, we plan to prospectively enroll stage III NPC patients from hospitals in China. The participants will receive 3 cycles of induction chemotherapy (GP regimen + Camrelizumab) followed by intensity-modulated radiation therapy. 2 cycles of concurrent chemotherapy will be administered during the radiotherapy. Patients' treatment response will be evaluated with MRI examination after 27 fractions of radiotherapy. If the treatment response after 27 fractions of radiotherapy is complete remission, the participants will be randomized into reduced-dose radiotherapy group and conventional-dose radiotherapy group. If the treatment response after 27 fractions of radiotherapy is not complete remission, the participants will be assigned to the unenrolled group. All the participants in the unenrolled group will receive conventional-dose radiotherapy. After the radiotherapy, all the participants will receive 9 cycles of Camrelizumab immunotherapy. Besides, all the participants in the unenrolled group will also receive metronomic adjuvant capecitabine chemotherapy for 1 year. The prognosis, complication, and quality of life will be compared between the reduced-dose radiotherapy group and the conventional-dose radiotherapy group.
Study Type
INTERVENTIONAL
1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 200 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 3 cycles till the end of IC. 2. Adjuvant PD-1 blocking antibody: every 3 weeks × 9 cycles; 200 mg, day 1.
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles.
Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles.
Locoregional failure-free survival (LRFFS)
Locoregional failure-free survival is measured from day of diagnosis until local or regional recurrence.
Time frame: 3-year
Overall survival (OS)
Overall survival is measured from day of diagnosis until death from any cause.
Time frame: 3 year
Failure-free survival (FFS)
Failure-free survival is measured from day of diagnosis until local recurrence, regional recurrence, distant failure, or death from any cause, whichever occurred first.
Time frame: 3 year
Distant failure-free survival (DFFS)
Distant failure-free survival is measured from day of diagnosis until distant failure.
Time frame: 3 year
Local failure-free survival (LFFS)
Local failure-free survival is measured from day of diagnosis until local recurrence.
Time frame: 3 year
Regional failure-free survival (RFFS)
Regional failure-free survival is measured from day of diagnosis until regional recurrence.
Time frame: 3 year
Incidence rate of investigator-reported radiotherapy-related complications
Time frame: Within (acute complication) / since (late complication) 90 days after the radiotherapy onset.
Incidence rate of patient-reported adverse events
Time frame: 3 year
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Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
593
1. Definitive IMRT, 30 fractions, 5 fractions/week, 1 fraction/day 2. Radiotherapy dose: pGTV: 6360cGy/30F; pCTV1: 5460cGy/30F; pCTV2: 4920cGy/30F.
1. Definitive IMRT, 33 fractions, 5 fractions/week, 1 fraction/day 2. Radiotherapy dose: pGTV: 6996cGy/33F; pCTV1: 6006cGy/33F; pCTV2: 5412cGy/33F.
Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles
Metronomic adjuvant capecitabine chemotherapy: 650 mg/m2 p.o. bid, 1 year, adminstration starts immediately after concurrent chemoradiotherapy.
Fujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
RECRUITINGDongguan People's Hospital
Dongguan, Guangdong, China
RECRUITINGThe First People's Hospital of Foshan
Foshan, Guangdong, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGThe Affiliated Panyu Central Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
RECRUITINGCancer Hospital of Shantou University Medical College
Shantou, Guangdong, China
RECRUITINGAffiliated Hospital of Guangdong Medical University
Zhanjiang, Guangdong, China
RECRUITINGGuangdong Nongken Central Hospital
Zhanjiang, Guangdong, China
RECRUITINGCancer Hospital of Guangxi Medical University
Nanning, Guangxi, China
RECRUITING...and 16 more locations
Quality of life (QoL): questionnaire
Time frame: Regular evaluation after 30 fractions of radiotherapy.