Neoadjuvant Therapy of GP Chemotherapy Combined With Tislelizumab in Locoregionally Advanced NPC

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Efficacy and Safety of of GP Chemotherapy Combined With Tislelizumab Neoadjuvant Therapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: a Single-arm, Phase 2 Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04833257
• Other study ID #: 2020-FXY-484
• Status: Recruiting
• Phase: Phase 2
• Start date: April 14, 2021
• Est. completion date: November 30, 2026

Study information

• Verified date: April 2021
• Source: Sun Yat-sen University
• Contact: Hai qiang Mai
• Phone: 86-20-87343380
• Email: maihq[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and tislelizumab in neoadjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

Description:

Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma(NPC). Gemcitabine plus cisplatin(GP) has been demonstrated an effective chemotherapy regimen for NPC patients in previous studies. The results of GP combined with concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma showed 10% of locoregionally advanced NPC patients had complete response after three cycles of GP neoadjuvant chemotherapy, and GP neoadjuvant chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as compared with chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based neoadjuvant chemotherapy in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Recently, immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1)monoclonal antibody has shown promising efficacy in the treatment of tumor patients. Clinical trials have shown objective response rates of 20.5%-34% in patients with recurrent or metastatic NPC patients receiving anti PD-1 monoclonal antibody immunotherapy including pembrolizumab, nivolumab, camrelizumab, and toripalimab. The current NCCN guidelines recommend anti PD-1 monoclonal antibody as a second-line treatment for recurrent or metastatic NPC. More and more evidence show that immunotherapy combined with chemotherapy has a synergistic effect in treating tumors. GP chemotherapy combined with anti PD-1 antibody has achieved the initial effect in NPC. Phase 1 trials have shown the combination of camrelizumab plus GP chemotherapy in recurrent or metastatic NPC led to a proportion of 91% patients achieving an objective response. Tislelizumab, approved by the National Medical Products Administration in China, is an anti-PD-1 monoclonal IgG4 antibody with higher affinity to PD-1 than pembrolizumab and nivolumab and was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Multiple clinical trials have shown strong anti-neoplastic activity of tislelizumab in various tumors including NPC. Clinical trial has shown an objective response rates of 43% in patients with recurrent metastatic nasopharyngeal carcinoma treated with tirelizumab, which is superior to other anti PD-1 monoclonal antibodys. So we hypothesize that GP neoadjuvant chemotherapy combined with tislelizumab could further improve survival of patients with locaregionally advanced NPC. Based on this, this study aims to evaluate the efficacy and safety of gemcitabine plus cisplatin chemotherapy combined with tislelizumab neoadjuvant therapy, followed by cisplatin based concurrent chemoradiotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for individualized comprehensive treatment in NPC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Voluntary participation with Written informed consent.

2. Age = 18 years and = 70 years, male or non-pregnant female.

3. Histologically or cytologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).

4. Original clinical staged as III-IVa (according to the 8th AJCC edition), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

5. White blood cell count (WBC)=4.0×109 /L, Hemoglobin = 90g/L, Platelet count =100×109/L.

6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) =2.0 times the upper limit of normal (ULN) .

7. Adequate renal function: creatinine clearance rate=60 ml/min .

Exclusion Criteria:

1. Patients with recurrent or metastatic nasopharyngeal carcinoma.

2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.

3. Prior therapy with Systemic chemotherapy.

4. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.

5. Seropositivity for human immunodeficiency virus (HIV).

6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).

7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.

8. Patients with immunodeficiency disease or a history of organ transplantation.

9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.

10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.

11. Patients with severe, uncontrolled disease or infections.

12. Received other research drugs or in other clinical trials at the same time.

13. Refuse or fail to sign the informed consent .

14. Patients with other treatment contraindications.

15. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.

16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) =1000cps/ml.

17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• GP combine with Tislelizumab neoadjuvant therapy+CCRT
chemotherapy combine with anti-PD-1 targeted immunotherapy+concurrent chemotherapy

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (7)

Desai J, Deva S, Lee JS, Lin CC, Yen CJ, Chao Y, Keam B, Jameson M, Hou MM, Kang YK, Markman B, Lu CH, Rau KM, Lee KH, Horvath L, Friedlander M, Hill A, Sandhu S, Barlow P, Wu CY, Zhang Y, Liang L, Wu J, Paton V, Millward M. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020 Jun;8(1). pii: e000453. doi: 10.1136/jitc-2019-000453. — View Citation

Economopoulou P, Kotsantis I, Psyrri A. The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches. ESMO Open. 2017 Feb 13;1(6):e000122. doi: 10.1136/esmoopen-2016-000122. eCollection 2016. Review. — View Citation

Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. — View Citation

Shen L, Guo J, Zhang Q, Pan H, Yuan Y, Bai Y, Liu T, Zhou Q, Zhao J, Shu Y, Huang X, Wang S, Wang J, Zhou A, Ye D, Sun T, Gao Y, Yang S, Wang Z, Li J, Wu YL. Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. J Immunother Cancer. 2020 Jun;8(1). pii: e000437. doi: 10.1136/jitc-2019-000437. Erratum in: J Immunother Cancer. 2020 Jul;8(2):. — View Citation

Zhang J, Fang W, Qin T, Yang Y, Hong S, Liang W, Ma Y, Zhao H, Huang Y, Xue C, Huang P, Hu Z, Zhao Y, Zhang L. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol. 2015 Mar;32(3):86. doi: 10.1007/s12032-015-0501-6. — View Citation

Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus — View Citation

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response	CR assessed by independent reviewers, according to the Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the neoadjuvant therapy. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) .	9 weeks
Secondary	Pathological Complete Response	Pathological complete response defined as the complete disappearance of the tumor cells in biopsy tissue of nasopharynx after neoadjuvant therapy .	9 weeks
Secondary	Overall Survival(OS)	The OS was defined as the duration from the date of registration to the date of death from any cause or censored at the date of the last follow-up.	2 years
Secondary	Progress-free survival(PFS)	Progress-free survival is calculated from the date of registration to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up	2 years
Secondary	Locoregional failure-free survival(LRRFS)	The LRRFS is evaluated and calculated from the date of registration until the day of first locoregional relapse or until the date of the last follow-up visit.	2 years
Secondary	Distant metastasis-free survival(DMFS)	The DMFS is evaluated and calculated from the date of registration until the day of first distant metastases or until the date of the last follow-up visit.	2 years
Secondary	Incidence rate of adverse events (AEs)	Analysis of treatment-related AEs (trAEs) and immune-related AEs (irAEs) are evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.	2 years
Secondary	PD-L1 expression level of tumor cell		2 years
Secondary	tumor-infiltrating lymphocytes (TILs)		2 year