This is a phase 3, multi-center, randomized controlled trial, with the purpose to evaluate the therapeutic efficacy and safety of PD-1 blockade (toripalimab) combined with the de-intensified chemoradiotherapy sparing concurrent cisplatin (i.e., toripalimab incorporated into induction chemotherapy and radiotherapy) in high-risk locoregionally advanced nasopharyngeal carcinoma.
This phase 3, multi-center, randomized controlled trial plans to enroll 532 patients with newly-diagnosed, pathologically-proven, untreated locoregionally advanced nasopharyngeal carcinoma (LANPC) at high-risk of distant metastasis (T4N1 and T1-4N2-3, according to American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\] 8th edition clinical staging system). Patients will receive 3 cycles of induction chemotherapy (IC; gemcitabine-cisplatin regimen) followed by 1) experimental arm (de-intensification group): intensity-modulated radiotherapy (IMRT) alone or 2) control arm (standard group): 2 cycles of concurrent cisplatin plus IMRT (CCRT). For both of the two arms, toripalimab will be adopted on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, with the first and last 3 cycles of toripalimab administrated along with IC and CCRT/IMRT, respectively. After three weeks of the completion of IMRT, adjuvant toripalimab will be used every 3 weeks for 11 cycles, and therefore the entire treatment process is expected to last for one year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
532
1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 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. IMRT phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 mg, day 1; start on day 1 of IMRT or CCRT and continue every 3 weeks for 3 cycles till the end of IMRT. 3. Adjuvant PD-1 blocking antibody: every 3 weeks × 11 cycles; 240 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
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, China
First People's Hospital of Foshan
Foshan, Guangdong, China
Failure-free survival (FFS)
Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first
Time frame: 3-year
Incidence rate of all-grade vomiting
Incidence rate of all-grade vomiting during treatment assessed by clinicians according to the Common Terminology Criteria for Adverse Events 5.0.
Time frame: Through study completion, an average of 1 year
Overall survival (OS)
Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive
Time frame: 3-year
Locoregional failure-free survival (LRFFS)
Locoregional failure-free survival is measured from day of diagnosis until local or regional recurrence
Time frame: 3-year
Distant failure-free survival (DFFS)
Distant failure-free survival is measured from day of diagnosis until distant metastasis
Time frame: 3-year
Incidence rate of investigator-reported adverse events (AEs)
Analysis of investigator-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0
Time frame: 3-year
Incidence rate of patient-reported adverse events (AEs)
Analysis of patient-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by patients themselves
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Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Panyu central hospital
Guangzhou, Guangdong, China
Cancer Hospital of Guangxi Medical University
Nanning, Guangxi, China
Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, China
Hubei Province Cancer Hosiptal
Wuhan, Hubei, China
Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Xiangya Hospital Central South University
Changsha, Hunan, China
...and 2 more locations
Time frame: 3-year
Quality of life (QoL): questionnaire
Changes in QoL of participants from initial treatment to 6 months after the completion of 6 cycles adjuvant PD-1 blocking antibody. QoL is evaluated with the use of (1) the head-and-neck-specific module (H\&N35) of the Quality of Life Questionnaire-Core 30 module (QLQ-C30), which is established by European Organization for Research and Treatment of Cancer (EORTC) and (2) the general and head-and-neck-specific module of the evaluation tool developed by the Functional Assessment of Cancer Therapy (FACT). Scores for the module range of H\&N35 QLQ-C30 from 0 to 100, with higher scores indicating better functioning or well-being or higher symptom burden (scales measuring symptom burden were reverse-scored to facilitate presentation)
Time frame: week 1, 20, 40, 64
Tumor response
Evaluation of tumor response (CR, PR, SD, PD, NA) performed after induction chemotherapy, radiotherapy, and adjuvant PD-1 immunotherapy.
Time frame: Through study completion, an average of 1 year