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

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: metronomic adjuvant chemotherapy with capecitabine

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 252
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: observation; observation after CCRT
Experimental: metronomic adjuvant chemotherapy with capecitabine; metronomic adjuvant chemotherapy with capecitabine after CCRT.	Drug: metronomic adjuvant chemotherapy with capecitabine; The concurrent chemoradiotherapy (CCRT) regimen consisted of IMRT delivering 69.96 Gy in 33 fractions, combined with cisplatin administered at 35-40 mg/m² weekly for 6 cycles to achieve a cumulative dose of ≥200 mg/m². During CCRT, plasma EBV DNA titer was monitored weekly. If EBV DNA remained undetectable from the second week after CCRT initiation until the end of radiotherapy, patients underwent observation after radiotherapy. If EBV DNA was detectable at any time point from the second week of CCRT until the end of radiotherapy, patients were randomized in a 1:1 ratio to observation or metronomic adjuvant chemotherapy with capecitabine (650 mg/m² twice daily, Q3W) for 8 cycles (6 months) after radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FFS	FFS is defined as the time from randomization to the first occurrence of local regional recurrence, distant metastasis, or death from any cause	3-year

Secondary Outcome Measures

Outcome Measure	Time Frame
DMFS	3-year
LRRFS	3-year
OS	3-year

Collaborators and Investigators

• Sponsor: Chongqing University Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2025
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Nasopharyngeal Carcinoma; EBV DNA; Metronomic Capecitabine
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine
• Other Study ID Numbers: CZLL2025-031-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Due to ethical considerations, contact us via email if needed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No