This randomized clinical trial determining whether Sintilimab plus Capecitabine versus Capecitabine alone can improve the progression-free survival rate of NPC patients with unfavorable response to induction chemotherapy. Patients whose plasma EBV DNA\> 0 copy/mL or SD/PD according to RECIST1.1 after two cycles induction chemotherapy will have concurrent chemoradiotherapy. MRI, CT and EBV DNA will be assessed before the end of radiotherapy. After concurrent chemoradiotherapy, eligible patients will be randomized to receive either adjuvant Sintilimab plus Capecitabine or Capecitabine alone.
Currently, although NCCN (National Comprehensive Cancer Network) guidelines recommend induction chemotherapy combined with concurrent chemoradiotherapy as IIA level-evidenced treatment for nasopharyngeal carcinoma (NPC), there are still about 20-30% of patients with NPC who experienced recurrence and metastasis after radical treatment. Our previous results showed that patients with plasma Epstein-Barr virus (EBV) DNA \> 0 copy/mL or stable disease/progressive disease (SD/PD) after induction chemotherapy had a significantly higher risk of disease progression than patients with plasma EBV DNA=0 copy/mL and complete response/partial response (CR/PR), according to Response Evaluation Criteria in Solid Tumors (RECIST). As for these high-risk patients, the urgent clinical problem to be solved is whether increased adjuvant treatment intensity after concurrent chemoradiotherapy can improve their survival rates. The addition of adjuvant capecitabine to chemoradiotherapy significantly improved survival in patients with NPC, with a manageable safety profile. Sintilimab is a humanized monoclonal antibody against programmed death 1(PD-1). Anti-PD-1 monoclonal antibody showed efficacy and safety in previous studies, however, the efficacy of immunotherapy alone was limited. Several prospective studies have shown that anti-PD-1 monoclonal antibody combined with chemotherapy had a synergistic effect. Based on this, this randomized clinical trial determining whether adjuvant Sintilimab plus Capecitabine versus Capecitabine alone can improve the progression-free survival rate of patients with unfavorable response to induction chemotherapy and may provide new evidence for individualized comprehensive treatment of NPC patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
Sintilimab is a humanized monoclonal antibody against Programmed death 1(PD-1).
An oral anticancer agent that can be converted into 5-Fu in vivo.
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGProgress-free survival (PFS)
Defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
Time frame: 2 years
Overall Survival (OS)
Defined as the time from random assignment to death from any cause or censored at the date of last follow-up
Time frame: 2 years
Locoregional Relapse-Free Survival (LRFS)
Defined as the time from random assignment to local or regional relapse, or death from any cause.
Time frame: 2 years
Distant Metastasis-Free Survival (DMFS)
Defined as the time from random assignment to distant metastasis, or death from any cause.
Time frame: 2 years
Incidence rate of adverse events (AEs)
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.
Time frame: 2 years
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TREATMENT
Masking
NONE
Enrollment
150