Concurrent Chemoradiotherapy With or Without Metronomic Capecitabine in High-Risk T1-2N1M0 NPC

Concurrent Chemoradiotherapy With or Without Metronomic Capecitabine in High-Risk T1-2N1M0 Nasopharyngeal Carcinoma: A Multicenter, Randomized Controlled, Phase III Clinical Study

This Phase III multicenter trial investigates treatment intensification for high-risk, stage T1-2N1M0 nasopharyngeal carcinoma. Patients with high-risk features (>3 metastatic lymph nodes, necrosis, or confluence) receive concurrent chemoradiotherapy. Those with detectable EBV DNA during radiotherapy are randomized 1:1 to adjuvant capecitabine or observation alone to assess efficacy and safety

This is a multicenter, randomized, phase III trial enrolling patients with AJCC/UICC 9th edition stage T1-2N1M0 nasopharyngeal carcinoma who have at least one of the following high-risk features: more than 3 metastatic cervical lymph nodes, presence of nodal necrosis, or presence of nodal confluence. All patients receive concurrent chemoradiotherapy (CCRT) with a weekly cisplatin regimen. Plasma EBV DNA is monitored weekly during CCRT. High-risk patients with detectable EBV DNA at any time from the second week of CCRT until the end of radiotherapy are randomized in a 1:1 ratio to receive either metronomic adjuvant chemotherapy with capecitabine or follow-up observation alone, to evaluate the efficacy and safety of treatment intensification

Inclusion Criteria:

1. Aged 18 to 70 years.
2. Pathologically confirmed, previously untreated "non-keratinizing carcinoma (WHO types II/III)" of the nasopharynx.
3. Diagnosed as stage T1-2N1M0 (Stage IB) according to the 9th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system.
4. Presence of at least one of the following high-risk lymph node features: more than three metastatic cervical lymph nodes (retropharyngeal lymph nodes are not counted), presence of nodal necrosis, or presence of nodal confluence.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Detectable baseline plasma EBV DNA, with EBV DNA remaining detectable at any time point from the second week after the start of concurrent chemoradiotherapy until the end of radiotherapy.
7. Adequate bone marrow function, liver and renal function.

Exclusion Criteria:

1. Intolerance or allergy to capecitabine.
2. Conditions that may interfere with the absorption or adherence to oral medication, such as dysphagia, chronic diarrhea, or intestinal obstruction.
3. Administration of biologic therapy or immunotherapy during or prior to radiotherapy.
4. Pregnancy or lactation (a pregnancy test should be considered for women of childbearing potential, and emphasis must be placed on effective contraception during the treatment period).
5. Any concurrent severe or uncontrolled medical condition that would pose an unacceptable risk or compromise protocol compliance, including but not limited to untreated unstable cardiac disease, renal disease, chronic hepatitis, poorly controlled diabetes (fasting blood glucose >1.5×ULN), or mood disorders.