Metronomic Capecitabine With or Without Tislelizuamb (PD-1 Antibody) as Adjuvant Therapy in High-risk Non-metastatic Nasopharyngeal Carcinoma: a Multicentre, Open-label, Randomised Phase 3 Trial

Sun Yat-sen University1 site in 1 country556 target enrollmentApril 17, 2022

ConditionsNasopharyngeal Carcinoma

InterventionsPD-1 antibody Capecitabine

DrugsPD-1 antibody Capecitabine

Overview

Phase: Phase 3
Intervention: PD-1 antibody
Conditions: Nasopharyngeal Carcinoma
Sponsor: Sun Yat-sen University
Enrollment: 556
Locations: 1
Primary Endpoint: failure-free survival
Status: Recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This trial is aimed to investigate whether additional adjuvant PD-1 antibody treatment could improve survival in high-risk nasopharyngeal carcinoma compared to metronomic capecitabine alone.

Detailed Description

In this multicenter, randomised controlled, phase 3 trial, patients with T4N+/TanyN2-3 (AJCC/UICC 8th system), or non-metastatic nasopharyngeal carcinoma with pretreatment EBV DNA \> 4000 copies/ml, will be randomized in a 1:1 ratio to receive metronomic capecitabine with or without PD-1 antibody every 3 weeks for 1 year after curative chemoradiation.

Registry

clinicaltrials.gov

Start Date

April 17, 2022

End Date

June 2029

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sun Yat-sen University

Responsible Party

Principal Investigator

Jun Ma, MD

Hospital Deputy Dean

Sun Yat-sen University

Eligibility Criteria

Inclusion Criteria

•Age at diagnosis: 18 \~ 65 years old;
•Pathologically confirmed primary nasopharyngeal carcinoma with "non-keratinizing carcinoma (WHO criteria)";
•Locoregionally advanced nasopharyngeal carcinoma (T4N + or TanyN2-3M0, or TanyNanyM0 pretreatment EBVDNA ≥ 4000 copies/mL) was diagnosed according to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition clinical staging system.
•Induction and concurrent chemoradiotherapy with the recommended regimen have been completed;
•ECOG score: 0 \~ 1 points (Appendix II);
•It is recommended to initiate adjuvant therapy within 1 month after the completion of the last radiotherapy treatment, no later than 6 weeks;
•Normal bone marrow function: white blood cell count \> 4 × 109/L, hemoglobin concentration \> 90 g/L, platelet count \> 100 × 109/L;
•Normal liver and kidney function: total bilirubin ≤ 1.5 times the upper limit of normal; aspartate aminotransferase and/or alanine aminotransferase ≤ 2.5 times the upper limit of normal; alkaline phosphatase ≤ 2.5 times the upper limit of normal; creatinine clearance ≥ 60 mL/min;
•Subjects must sign the informed consent form, and must be willing and able to comply with the visits, treatment regimen, laboratory tests and other requirements specified in the study protocol;
•Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use reliable contraception (e.g., condoms, regular contraceptives as directed) from screening through 1 year after treatment.

Exclusion Criteria

•Positive hepatitis B surface antigen and hepatitis B virus quantification \> 1 × 1000 copies/ml, or positive anti-hepatitis C virus antibody;
•Positive anti-HIV antibody or diagnosis of acquired immunodeficiency syndrome (i.e., AIDS);
•Conditions such as dysphagia, chronic diarrhea, or bowel obstruction that would interfere with oral medication.
•Patients with severe chronic or active infection that must be treated with systemic antibacterial, antifungal or antiviral therapy before randomization, including but not limited to tuberculosis infection
•Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, hypothyroidism, and asthma requiring bronchiectasis). Except for type I diabetes, hypothyroidism requiring hormone replacement therapy and skin diseases not requiring systemic treatment (such as vitiligo, psoriasis or alopecia); clinicians should perform necessary history, examination and examination before enrollment for the above diseases and then exclude them;
•Interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy within 1 year;
•Definite clinical evidence of persistent local disease or distant metastasis after chemoradiotherapy;
•Systemic hormonal or other immunosuppressive therapy with an equivalent dose of \> 10 mg prednisone/day within 28 days prior to informed consent. Subjects with systemic sex hormone doses ≤ 10 mg prednisone/day or inhaled/topical corticosteroids may be included.
•Uncontrolled heart disease, such as: 1) heart failure, NYHA level ≥ 2; 2) unstable angina; 3) history of myocardial infarction in the past year; 4) supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
•Pregnant or lactating women (pregnancy test should be considered for sexually active women of childbearing age);

Arms & Interventions

Metronomic Capecitabine with PD-1 antibody arm

Patients randomised to this arm will receive metronomic capecitabine (650mg/m2, BID, PO) and Tislelizuamb (200mg, iv drip, Q3W) for 1 year as adjuvant therapy, beginning 4-6 weeks after chemoradiation.

Intervention: PD-1 antibody

Metronomic Capecitabine with PD-1 antibody arm

Intervention: Capecitabine

Metronomic Capecitabine alone arm

Patients randomised to this arm will receive metronomic capecitabine (650mg/m2, BID, PO) alone for 1 year as adjuvant therapy, beginning 4-6 weeks after chemoradiation.

Intervention: Capecitabine