This is a phase 2, single-arm, multicenter clinical trial, with the purpose to evaluate the therapeutic efficacy, safety, and tolerability of PD-1 Blockade nivolumab combined with a deintensified chemoradiotherapy by sparing concurrent cisplatin from the standard induction chemotherapy plus concurrent chemoradiotherapy in high-risk locoregionally advanced nasopharyngeal carcinoma.
This phase 2, single-arm, multicenter clinical trial plans to enroll 152 patients with newly-diagnosed, pathologically-proven, untreated locoregionally advanced nasopharyngeal carcinoma (LANPC) at high-risk of distant metastasis (T4N1M0 or T1-4N2-3M0, 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 intensity-modulated radiotherapy (IMRT) alone. Nivolumab injection OPDIVO® will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. The first and last 3 cycles of nivolumab are administrated concurrently with IC and IMRT, respectively. After the completion of IMRT, adjuvant nivolumab will begin every 4 weeks for 6 cycles.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
152
1. Whole-course concurrent PD-1 blocking antibody: every 3 weeks × 6 cycles; 360 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. 2. Adjuvant PD-1 blocking antibody: every 4 weeks × 6 cycles; 480 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
Fujian Provinve Cancer Hospital
Fuzhou, Fujian Provinve, China
Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, China
Hubei Province Cancer Hosiptal
Wuhan, Hubei, China
Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Failure-free survival (FFS)
Failure-free survival is measured from day of enrollment until the first indication of treatment failure (either locoregional recurrence or distant metastasis) or death from any cause, whichever occurred first
Time frame: 3-year
Overall survival (OS)
Overall survival is measured from day of enrollment 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 enrollment until local or regional recurrence
Time frame: 3-year
Distant failure-free survival (DFFS)
Distant failure-free survival is measured from day of enrollment 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 the PRO-CTCAE. Tolerability profiles are evaluated by patients themselves.
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)
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Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Xiangya Hospital Central South University
Changsha, Hunan, China
Zhejiang Province Cancer Hospital
Hangzhou, Zhejiang, China
Time frame: baseline, week 7, 14, 38, 62