The CONTINUUM trial plans to enroll patients with stage III-IVA (AJCC 8th, except T3N0-1 or T4N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus Sintilimab. All patients will receive intensity-modulated radiotherapy (IMRT). Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 12 cycles.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
425
Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.
Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.
Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
First People's Hospital of Foshan
Foshan, Guangdong, China
Panyu central hospital
Guangzhou, Guangdong, China
SUN YAT-SEN UNIVERSITY cANCER CENTER
Guangzhou, Guangdong, China
Cancer Hospital of Guangxi Medical University
Event-free survival (EFS)
calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
Time frame: 3 years
Overall survival (OS)
calculated from randomization to the date of death from any cause.
Time frame: 3 years
Distant metastasis-free survival (DMFS)
calculated from randomization to the date of first distant metastasis, or death from any cause, whichever occurred first.
Time frame: 3 years
Locoregional recurrence-free survival (LRFS)
calculated from randomization to the date of locoregional persistence, 1st locoregional recurrence, or death from any cause, whichever occurred first.
Time frame: 3 years
Adverse events (AEs) and serious adverse events (SAEs)
Graded according to CTCAE V5.0.
Time frame: 3 years
Quality of life (QoL)
The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 34 weeks (at the end of sintilimab treatment in the sintilimab arm and the corresponding timepoint in the chemoradiation arm), 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30)version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.
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Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Nanning, Guangxi, China
Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, 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
Xijing Hospital, Fourth Military Medical University
Xi’an, Shanxi, China
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Time frame: 3 years
Event-free survival (EFS) within different subgroups
analyses for EFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (\<4000copies/ml vs. ≥4000copies/ml), different PD-L1 expression levels (\<1% vs. ≥1%), tertiary lymphoid structure (+ vs. -), age, gender, performance status, T category, N category, and stage (III vs. IVA).
Time frame: 3 years