This single-arm, phase 2 trial evaluates the efficacy and safety of de-escalated radiotherapy (restricted to the primary tumor, omitting prophylactic neck irradiation) combined with neoadjuvant and adjuvant toripalimab immunotherapy, and concurrent chemotherapy in patients with nasopharyngeal carcinoma staged N0 or N1, where nodal involvement is strictly confined to the retropharyngeal lymph nodes.
The goals of this clinical trial includes: ① To assess the regional relapse-free survival (RRFS) and safety after radiotherapy without prophylactic neck irradiation in combination with neoadjuvant and adjuvant PD-1 antibody toripalimab and cisplatin concurrent chemotherapy for N0-1 (restricted to retropharyngeal lymph nodes) patients with nasopharyngeal carcinoma; ② To evaluate the impact of radiotherapy without prophylactic neck irradiation on 2-year overall survival (OS), 2-year progress-free survival (PFS), 2-year distant metastasis-free survival (DMFS), and 2-year locoregional relapse-free survival (LRRFS) for N0-1 ( limited to retropharyngeal lymph nodes) patients with nasopharyngeal carcinoma; ③ To explore the impact of radiotherapy without prophylactic neck irradiation on toxicities and quality of life; ④ To explore the relationship between clinical factors and the impact of neoadjuvant and adjuvant PD-1 antibody, radiotherapy without prophylactic neck irradiation on the survival of patients; ⑤ To explore the biomarkers of sensitivity to immunotherapy, chemotherapy and radiotherapy for patients with nasopharyngeal carcinoma and the underlying mechanism. For these purposes, we plan to prospectively enroll T2N0-1 and primary gross tumor volume (GTV) greater than 30.0 cm3 or T3-4N0-1 stage NPC patients, whose N1 restricted to retropharyngeal lymph nodes from one center in China. The patients will receive 2 cycles of neoadjuvant PD-1 antibody (toripalimab monotherapy, 240 mg, every two weeks, intravenous infusion) followed by concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy (IMRT), and adjuvant toripalimab (240 mg intravenously) once every 3 weeks for up to eight cycles. All participants will be treated with IMRT restricted to primary tumor without prophylactic neck irradiation. The clinical outcomes, safety, complications, and quality of life will be explored in the RT without prophylactic neck irradiation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
59
Intensity-modulated radiotherapy restricted to the primary tumor, omitting prophylactic neck irradiation.
Toripalimab 240mg every 2 weeks with a total of 2 cycles as neoadjuvant anti-PD-1 immunotherapy; Toripalimab 240mg every 3 weeks with a total of 8 cycles as adjuvant anti-PD-1 immunotherapy after CCRT
Cisplatin 100mg/m2(every three weeks), Day 1, Day 22, Day 43 of intensity modulated radiotherapy
Sun Yat-sen Universitty Cancer Center
Guangzhou, Guangdong, China
Regional relapse-free survival (RRFS)
Defined as the time from registration to documented nodal relapse or non-cancer-specific death.
Time frame: 2 years
Progress-free survival (PFS)
Defined as the time from registration to documented disease progression or non-cancer-specific death.
Time frame: 2 years
Overall Survival (OS)
Defined as the time from registration to death from any cause.
Time frame: 2 years
Locoregional Relapse-Free Survival (LRRFS)
Defined as the time from registration to documented locoregional recurrence or non-cancer-specific death.
Time frame: 2 years
Distant Metastasis-Free Survival (DMFS)
Defined from registration to documented distant metastasis or noncancer-specific death.
Time frame: 2 years
Objective Response Rate (ORR)
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI).
Time frame: After the completion of the neoadjuvant PD-1 antibody and chemoradiotherapy treatment
Incidence rate of acute and late adverse events (AEs)
Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. Acute AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE 5.0). Late radiation toxicities were assessed using the Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC).
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Time frame: 2 years
Change of QoL (quality of life)
QoL scores were assessed by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) and Quality-of-Life Head and Neck 35 items (QLQ-H\&N35) before neoadjuvant PD-1 antibody, before radiotherapy, at the end of radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy.
Time frame: 1 year