Peramprizumab Combined With GP ± Anlotinib as Neoadjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Peramprizumab Combined With GP ± Arotinib Induction Therapy + Concurrent Chemoradiotherapy + Adjuvant Peramprizumab in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05193617
• Other study ID #: 2021-FXY-504
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 20, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: January 2022
• Source: Sun Yat-sen University
• Contact: Hai-Qiang Mai, Ph.D
• Phone: 8613570027338
• 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 Peramprizumab ± Anlotinib in neoadjuvant therapy combined with Peramprizumab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

Description:

Radiotherapy combined with chemotherapy is the standard treatment method for locally advanced NPC. In the 2020 National Comprehensive Cancer Network (NCCN) guidelines, GP regimen induction chemotherapy combined with concurrent chemoradiotherapy has been established as evidence-based grade 2A.

Based on the results of phase 3 clinical trials, the addition of PD-1 monoclonal antibody to GP chemotherapy as a first-line treatment for patients with recurrent or metastatic nonkeratinizing NPC provided superior PFS, ORR and DoR than GP alone while maintaining a manageable safety profile. Therefore, the combination of PD-1 monoclonal antibody in GP induction chemotherapy may further improve the prognosis of patients with locally advanced NPC.

There is a complex interaction between tumor immune microenvironment and tumor vascular remodeling. Anti-PD-1 monoclonal antibody combined with anti-VEGF have synergistic effect and inhibit tumor growth.

Peramprizumab is a new type of PD-1 monoclonal antibody. It has the characteristics of strong antigen binding and slow dissociation rate, which can maintain the antitumor activity of T cells.

Anlotinib is a multi-target tyrosine kinase inhibitor (TKI). It can effectively inhibit a variety of receptors, including vascular endothelial growth factor receptor (VEGFR), and block tumor angiogenesis more comprehensively.

Based on the above research background, this study adopts a two-stage design:

Stage I (Pick the Winner Study): For patients with locally advanced NPC, the complete response rate (CR) of tumor after induction chemotherapy was compared between the two groups of patients receiving GP + peramprizumab and GP + peramprizumab + arotinib before radiotherapy. The regimen with higher CR rate was the winner at this stage.

Stage II ( Cohort Expansion Study): The 3-year failure free survival (FFS) of patients in the winning regimen of expansion cohort was calculated through long-term follow-up and compared with the data in previous trials.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Voluntary participation with Written informed consent.

2. Age = 18 years and = 65 years, male or non-pregnant female.

3. Histologically 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),exclude T3-4N0, T3N1(Only retropharyngeal lymph nodes metastasized), 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 or Creatinine =1.5× upper limit of normal value.

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+Peramprizumab+Anlotinib
GP combine with peramprizumab and anlotinib neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy
• GP+Peramprizumab
GP combine with peramprizumab neoadjuvant therapy+CCRT+peramprizumab adjuvant therapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

References & Publications (2)

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. — 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, 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1(Pick the Winner Study): Complete Response	The proportion of patients who had a complete response was defined as those with all pathological cervical lymph nodes being less than 10 mm in the short axis and no unequivocal soft tissue mass in the local region. Disease response was evaluatedby by the Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) 95% confidence intervals (CIs) were calculated using the Clopper Pearson method	9 weeks
Primary	Stage 2 (Cohort Expansion Study): Failure-free survival (FFS)	Defined as the time from registration to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.	3 years
Secondary	Overall survival (OS)	Defined as the time from registration to death from any cause or censored at the date of last follow-up.	3 years
Secondary	Locoregional failure-free survival (LRRFS)	Defined as the time from registration to local or regional relapse, or death from any cause.	3 years
Secondary	Distant metastasis-free survival (DMFS)	Defined as the time from registration to distant metastasis, or death from any cause.	3 years
Secondary	Incidence rate of adverse events (AEs)	Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.	3 years
Secondary	Objective Response Rate (ORR)	Objective response rate (ORR) was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.	9 weeks