Metronomic Capecitabine With or Without PD-1 Antibody as Adjuvant Therapy in High-risk Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05342792
• Other study ID #: SL-B2022-202-02
• Status: Recruiting
• Phase: Phase 3
• Start date: April 17, 2022
• Est. completion date: June 2029

Study information

• Verified date: April 2022
• Source: Sun Yat-sen University
• Contact: Jun Ma, MD
• Phone: +862087343469
• Email: majun2[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 556
• Est. completion date: June 2029
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age at diagnosis: 18 ~ 65 years old;

2. Pathologically confirmed primary nasopharyngeal carcinoma with "non-keratinizing carcinoma (WHO criteria)";

3. 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.

4. Induction and concurrent chemoradiotherapy with the recommended regimen have been completed;

5. ECOG score: 0 ~ 1 points (Appendix II);

6. It is recommended to initiate adjuvant therapy within 1 month after the completion of the last radiotherapy treatment, no later than 6 weeks;

7. Normal bone marrow function: white blood cell count > 4 × 109/L, hemoglobin concentration > 90 g/L, platelet count > 100 × 109/L;

8. 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;

9. 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;

10. 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:

1. Positive hepatitis B surface antigen and hepatitis B virus quantification > 1 × 1000 copies/ml, or positive anti-hepatitis C virus antibody;

2. Positive anti-HIV antibody or diagnosis of acquired immunodeficiency syndrome (i.e., AIDS);

3. Conditions such as dysphagia, chronic diarrhea, or bowel obstruction that would interfere with oral medication.

4. 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

5. 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;

6. Interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy within 1 year;

7. Definite clinical evidence of persistent local disease or distant metastasis after chemoradiotherapy;

8. 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.

9. 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;

10. Pregnant or lactating women (pregnancy test should be considered for sexually active women of childbearing age);

11. Previous or current other malignancy other than adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma;

12. Receipt of live vaccines within 30 days prior to the first course of tislelizumab;

13. History of organ transplantation;

14. Other conditions that may jeopardize patient safety or compliance as assessed by the investigator, such as serious illness (including psychiatric disorders) requiring prompt treatment, severely abnormal test results, and other family or social risk factors.

15. Patients who received surgical treatment, biological therapy, or immunotherapy during or before radiotherapy;

16. Patients who are receiving or are likely to receive other chemotherapy, biological therapy, or immunotherapy History of severe hypersensitivity to other monoclonal antibodies;

17. Chemotherapy or surgery (except diagnostic) of the primary tumor or lymph nodes before standard treatment.

18. History of radiation therapy prior to standard therapy (except for non-melanoma skin cancer).

19. Patients who are known to be intolerable or sensitive to any therapeutic agents.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• PD-1 antibody
Tislelizumab:200 mg per dose, intravenous infusion over 30 minutes, every 3 weeks as a cycle for 17 cycles after concurrent chemoradiotherapy
• Capecitabine
Capecitabine : 650 mg/m2 bid, orally, d1-21, every 3 weeks as a cycle for 17 cycles after concurrent chemoradiotherapy

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (13)

Lead Sponsor

Collaborator

Sun Yat-sen University

Affiliated Cancer Hospital of Guizhou Medical University, Cancer Hospital of Guangxi Medical University, Chongqing University Cancer Hospital, Fifth Affiliated Hospital, Sun Yat-Sen University, First People's Hospital of Foshan, Hubei Cancer Hospital, Hunan Cancer Hospital, Shandong Provincial Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Tongji Hospital, Wuhan Union Hospital, China, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	failure-free survival	calculated from the date of randomisation to the date of locoregional failure, distant failure, or death from any cause, whichever occurred first	3 years
Secondary	overall survival	calculated from date of randomisation to death	5 years
Secondary	distant metastasis-free survival	calculated from date of randomisation to the first distant failure	3 years
Secondary	locoregional recurrence-free survival	locoregional recurrence-free survival	3 years
Secondary	adverse events (AEs) and severe adverse events (SAE)	graded according to NCI CTCAE v5.0	5 years
Secondary	quality of life (QoL)	the change of QoL from randomization to 12 months after chemoradiation, graded according to EORTC QLQ-C30 V3.0	3 years