Neoadjuvant and Adjuvant Tislelizumab for Nasopharyngeal Carcinoma

NCT05211232 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 2021-FXY-452
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Complete Response

  CR assessed by investigator, according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) 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

• Progression-free Survival (PFS)

  defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (4)

• Overall Survival(OS)

  3 years

• Locoregional failure-free survival(LRRFS)

  3 years

• Distant metastasis-free survival(DMFS)

  3 years

• Number of participants with adverse events

  up to 3 years

Study Arms (2)

GP combined with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

EXPERIMENTAL

Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and tislelizumab(200mg) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) ,then followed by adjuvant therapy with tislelizumab(200mg) every three weeks for eight cycles after radiotherapy

Drug: Tislelizumab

GP combine with Placebo neoadjuvant therapy+CCRT+Placebo adjuvant therapy

PLACEBO COMPARATOR

Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and Placebo(200mg) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) ,then followed by adjuvant therapy with Placebo(200mg) every three weeks for eight cycles after radiotherapy

Drug: Placebo

Interventions

Tislelizumab DRUG

GP combine with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

Also known as: BGB-A317

GP combined with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

Placebo DRUG

GP combine with Placebo neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

GP combine with Placebo neoadjuvant therapy+CCRT+Placebo adjuvant therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be informed of the investigational nature of this study and give written informed consent.
• Age ≥ 18 years and ≤70 years,men or non-pregnant women.
• Patients with histologically confirmed Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
• Tumor staged as III-IVA (AJCC 8th, except T3N0，T3N1(Only retropharyngeal lymph nodes metastasized).
• No previous anti-tumor treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Adequate marrow function:White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.

You may not qualify if:

• Patients with recurrent or metastatic nasopharyngeal carcinoma.
• Histologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
• Prior therapy with radiation or systemic chemotherapy.
• Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
• Seropositivity for human immunodeficiency virus (HIV).
• Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
• Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
• Patients with immunodeficiency disease or a history of organ transplantation.
• Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
• Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
• Patients with severe, uncontrolled disease or infections.
• Received other research drugs or in other clinical trials at the same time.
• Refuse or fail to sign the informed consent .
• Patients with other treatment contraindications.
• Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Cancer Hospital of Guizhou Province: collaborator
• Hunan Cancer Hospital: collaborator
• Wuzhou Red Cross Hospital: collaborator
• Affiliated Hospital of Guangdong Medical University: collaborator

Study Sites (4)

The Affiliated Hospital of Guangdong Medical College

Zhanjiang, Guangdong, China

Location

Wuzhou Red Cross Hospital

Wuzhou, Guangxi, China

Location

Guizhou Cancer Hospital

Guiyang, Guizhou, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Related Publications (4)

• 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, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

  PMID: 31150573 RESULT

• Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.

  PMID: 34341578 RESULT

• 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):e000437. doi: 10.1136/jitc-2019-000437.

  PMID: 32561638 RESULT

• Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2020 Sep 1;26(17):4542-4550. doi: 10.1158/1078-0432.CCR-19-3561. Epub 2020 Jun 19.

  PMID: 32561664 RESULT

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• haiqiang Mai, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 27, 2022
• Study Start: June 10, 2022
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2028
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)