Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin for LA-NPC.

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Prospective, Single-arm, Phase II Study of Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin in Locally Advanced Nasopharyngeal Carcinoma.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06059261
• Other study ID #: Lance
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2023
• Est. completion date: October 1, 2027

Study information

• Verified date: September 2023
• Source: Chongqing University Cancer Hospital
• Contact: Xin Zhang, Ph.D, M.D.
• Phone: 18323063006
• Email: zhangxin9964[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-center, prospective, single-arm, phase II clinical study, with the purpose to evaluate the therapeutic efficacy and safety of envafolimab combined with chemoradiotherapy and recombinant human endostatin in patients with locally advanced nasopharyngeal carcinoma.

Description:

Patients with locally advanced nasopharyngeal carcinoma will receive 3 cycles of induction therapy with envafolimab combined with recombinant endostatin and gemcitabine and cisplatin, followed by 2 cycles of sequential envafolimab and recombinant human endostatin combined with radiotherapy alone in the low-risk group (with undetectable EBV DNA and CR/PR after induction therapy), or 2 cycles of sequential envafolimab and recombinant human endostatin combined with concurrent chemoradiotherapy in the high-risk group (with detectable EBV DNA or SD/PD after induction therapy), and finally 5 cycles of adjuvant therapy with envafolimab.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. ECOG score 0-1.

2. Aged 18-65 years, male or non-pregnant female;

3. Pathologically confirmed diagnosis of nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, WHO type II or III) without the need to detect MSI and dMMR status.

4. Stage III-IVA (8th AJCC/UICC), including T1-2 N2-3/T3N1-3/T4N0-3, treatment-naive nasopharyngeal carcinoma patients.

5. MRI data of nasopharynx and neck before enrollment, and measurable lesions;

6. Agree to provide a previously stored tumor tissue specimen or biopsy to collect tumor lesion tissue and send it to the central laboratory for PD-L1 IHC testing.

7. Agree to undergo EBV antibody and EBV-DNA quantitative testing before receiving treatment.

8. Hematology: WBC = 4000/µL, neutrophils = 2.000/µL, hemoglobin = 9 g/dL, platelets = 100,000/µL;

9. Liver function: ALT, AST < 1.5 times the upper limit of normal (ULN), total bilirubin < 1.5 × ULN;

10. Renal function: serum creatinine < 1.5 × ULN.

11. Patients have signed the informed consent form and are willing and able to comply with the study plan visits, treatment plan, laboratory tests and other study procedures;

Exclusion Criteria:

1. Patients with recurrent nasopharyngeal carcinoma and distant metastasis.

2. Pathology was keratinizing squamous cell carcinoma (WHO classification type I).

3. Patients who have undergone radiotherapy or systemic chemotherapy;

4. Pregnant or lactating women, in the reproductive period without effective contraceptive measures;

5. HIV positive.

6. Having had other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);

7. Patients who have been treated with inhibitors of immune regulatory points (CTLA-4, PD-1, PD-L1, etc.);

8. Patients need long-term use of immunosuppressive drug therapy, or systemic or local use of immunosuppressive doses of corticosteroids complications;

9. Patients with immunodeficiency disease, history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood, without any intervention after adulthood can be included; patients with asthma requiring bronchodilators for medical intervention can not be included;

10. Use of excessive doses of glucocorticoids within 4 weeks.

11. Laboratory test values within 7 days before enrollment do not meet the relevant criteria;

12. Patients with significantly low heart, liver, lung, kidney and bone marrow function.

13. Any other diseases or conditions are contraindications to recombinant human vascular endothelial inhibitors, chemoradiotherapy, immunotherapy (such as active phase of infection, within 6 months after myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy);

14. Any arterial thrombosis, embolism or ischemia within 6 months before inclusion for treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack;

15. Severe, uncontrolled medical illness and infection.

16. Concurrent use of other investigational drugs or ongoing other clinical trials;

17. Refusing or unable to sign the informed consent form to participate in the trial.

18. Personality or mental disorders, no civil capacity or limited civil capacity;

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

20. Patients who tested positive for HCV antibody were included in the study only if they tested negative for HCV RNA by polymerase chain reaction.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Envafolimab and recombinant human endostatin combined with chemoradiotherapy
Induction treatment phase:Envafolimab administered by subcutaneous injection on day 1 every 3 weeks at 300 mg for 3 cycles, cisplatin administered by intravenous infusion on day 1 of each cycle at 80 mg/m2 every 3 weeks for 3 cycles, gemcitabine was administered by intravenous infusion on days 1 and 8 of each cycle at 1 g/m2 every 3 weeks for 3 cycles, recombinant human endostatin was administered on day 1 every 3 weeks at 210 mg for 3 cycles. Concurrent treatment phase: Envafolimab was administered by subcutaneous injection on day 1 every 3 weeks at 300 mg for 2 cycles. For high risk group, cisplatin was administered by intravenous infusion on day 1 of each cycle at 100mg/m2 every 3 weeks for 2 cycles, for low risk group, there is no need for chemotherapy. Adjuvant treatment Phase: Envafolimab was administered on day 1 every 3 weeks at 300 mg for 5 cycles as a subcutaneous injection. Intensity-modulated radiotherapy: 69.96Gy/33fractions/7weeks,5 fractions/week, 1 fraction/day.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing University Cancer Hospital

References & Publications (15)

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Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:150-158. doi: 10.1016/j.ejca.2017.01.002. Epub 2017 Feb 22. — View Citation

Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7. — View Citation

Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019 Jul 6;394(10192):64-80. doi: 10.1016/S0140-6736(19)30956-0. Epub 2019 Jun 6. — View Citation

Guan Y, Li A, Xiao W, Liu S, Chen B, Lu T, Zhao C, Han F. The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma. Oncotarget. 2015 Oct 20;6(32):33926-34. doi: 10.18632/oncotarget.5271. — View Citation

Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, Yu BK, Chiu SK, Kwan WH, Ho R, Chan I, Ahuja AT, Zee BC, Chan AT. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009 Jan 10;27(2):242-9. doi: 10.1200/JCO.2008.18.1545. Epub 2008 Dec 8. — View Citation

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Jiang XD, Dai P, Wu J, Song DA, Yu JM. Inhibitory effect of radiotherapy combined with weekly recombinant human endostatin on the human pulmonary adenocarcinoma A549 xenografts in nude mice. Lung Cancer. 2011 May;72(2):165-71. doi: 10.1016/j.lungcan.2010.09.003. Epub 2010 Oct 20. — View Citation

Li XY, Chen QY, Sun XS, Liu SL, Yan JJ, Guo SS, Liu LT, Xie HJ, Tang QN, Liang YJ, Wen YF, Guo L, Mo HY, Chen MY, Sun Y, Ma J, Tang LQ, Mai HQ. Ten-year outcomes of survival and toxicity for a phase III randomised trial of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma. Eur J Cancer. 2019 Mar;110:24-31. doi: 10.1016/j.ejca.2018.10.020. Epub 2019 Feb 7. — View Citation

Mao YP, Xie FY, Liu LZ, Sun Y, Li L, Tang LL, Liao XB, Xu HY, Chen L, Lai SZ, Lin AH, Liu MZ, Ma J. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009 Apr 1;73(5):1326-34. doi: 10.1016/j.ijrobp.2008.07.062. Epub 2009 Jan 17. — View Citation

Peng H, Chen L, Zhang J, Li WF, Mao YP, Zhang Y, Liu LZ, Tian L, Lin AH, Sun Y, Ma J. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy. J Cancer. 2017 Feb 10;8(3):371-377. doi: 10.7150/jca.16732. eCollection 2017. — View Citation

Sun X, Su S, Chen C, Han F, Zhao C, Xiao W, Deng X, Huang S, Lin C, Lu T. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2014 Mar;110(3):398-403. doi: 10.1016/j.radonc.2013.10.020. Epub 2013 Nov 11. — View Citation

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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 cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23. Erratum In: Lancet. 2016 Oct 15;388(10054):1882. — 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

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress-free survival (PFS)	Defined as the time interval from randomization to tumor progression or death due to any cause. The appearance of new lesions was used as a criterion for progression, and the landmark time point of progression was the date when measurable new lesions were first observed.	3 years
Secondary	Overall survival (OS)	Overall survival is measured from randomization until death due to any cause or the latest known date alive.	3 years
Secondary	Recurrence-free survival(RFS)	Defined as the time from randomization to documented disease recurrence (distant metastasis or local disease recurrence) or death from any cause, whichever occurs first.	3 years
Secondary	Locoregional Relapse-Free Survival (LRFS)	Defined as the time interval from randomization to the first occurrence of recurrence, or to the last follow-up time if there was no recurrence.	3 years
Secondary	Distant metastases-Free survival (DMFS)	Defined as the time interval from randomization to the occurrence of distant metastasis after treatment, or the time to the last follow-up or death due to other causes if there was no distant metastasis.	3 years
Secondary	Incidence rate of adverse events (AEs)	Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs, according to the Common Terminology Criteria for Adverse Events, version 5.0.	3 years
Secondary	Compliance	Refers to patients taking the drug according to the prescribed dose and course of treatment, as well as the degree of compliance with the study protocol during the implementation by the investigator.	3 years