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

Official title

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

Overview

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

Detailed description

This is a single-center, prospective, single-arm phase II clinical study. Patients with high-risk locally advanced stage III-IVA (8th AJCC/UICC staging) primary nasopharyngeal carcinoma, i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.) are enrolled. After being screened to meet the enrolment criteria and signing the informed consent form, they will receive 3 cycles of induction therapy with envafolimab combined with recombinant human vascular endothelial inhibitor and gemcitabine and cisplatin, followed by cisplatin-concomitant radiotherapy, and 8 cycles of adjuvant therapy with envafolimab after radiotherapy.

Interventions

• 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: Cisplatin was administe

Primary outcome measures

• Complete Response Rate (CRR) after Induction Therapy [Time frame: From enrollment to the end of induction therapy at 12 weeks]

Secondary outcome measures (6)

• Objective Response Rate (ORR) after Induction Therapy [Time frame: From enrollment to the end of induction therapy at 12 weeks]
• Progression Free Survival (PFS) [Time frame: 2 years]
• Overall survival (OS) [Time frame: 2 years]
• Locoregional Relapse-Free Survival (LRRFS) [Time frame: 2 years]
• Distant metastases-Free survival (DMFS) [Time frame: 2 years]
• Incidence rate of adverse events (AEs) [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• ECOG score 0-1.
• Aged 18-65 years, male or non-pregnant female;
• 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.
• high-risk locally advanced stage III-IVA (8th AJCC/UICC staging), i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.), treatment-naive nasopharyngeal carcinoma patients.
• MRI data of nasopharynx and neck before enrollment, and measurable lesions;
• 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.
• Agree to undergo EBV antibody and EBV-DNA quantitative testing before receiving treatment.
• Hematology: WBC ≥ 4000/μL, neutrophils ≥ 2.000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL;
• Liver function: ALT, AST < 1.5 times the upper limit of normal (ULN), total bilirubin < 1.5 × ULN;
• Renal function: serum creatinine < 1.5 × ULN.
• 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

• Patients with recurrent nasopharyngeal carcinoma and distant metastasis.
• Pathology was keratinizing squamous cell carcinoma (WHO classification type I).
• Patients who have undergone radiotherapy or systemic chemotherapy;
• Pregnant or lactating women, in the reproductive period without effective contraceptive measures;
• HIV positive.
• Having had other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
• Patients who have been treated with inhibitors of immune regulatory points (CTLA-4, PD-1, PD-L1, etc.);
• Patients need long-term use of immunosuppressive drug therapy, or systemic or local use of immunosuppressive doses of corticosteroids complications;
• 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;
• Use of excessive doses of glucocorticoids within 4 weeks.
• Laboratory test values within 7 days before enrollment do not meet the relevant criteria;
• Patients with significantly low heart, liver, lung, kidney and bone marrow function.
• 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);
• 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;
• Severe, uncontrolled medical illness and infection.
• Concurrent use of other investigational drugs or ongoing other clinical trials;
• Refusing or unable to sign the informed consent form to participate in the trial.
• Personality or mental disorders, no civil capacity or limited civil capacity;
• Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000cps/ml.
• Patients who tested positive for HCV antibody were included in the study only if they tested negative for HCV RNA by polymerase chain reaction.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Chongqing University Cancer Hospital — Chongqing

Publications

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• 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. PMID 31178151
• 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(100 PMID 27567279
• 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. PMID 19153016
• 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. PMID 30739837
• Au KH, Ngan RKC, Ng AWY, Poon DMC, Ng WT, Yuen KT, Lee VHF, Tung SY, Chan ATC, Sze HCK, Cheng ACK, Lee AWM, Kwong DLW, Tam AHP. Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study). Oral Oncol. 2018 Feb;77:16-21. doi: 10.1016/j.oraloncology.2017.12.004. Epub 2017 Dec 12. PMID 29362121
• 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. PMID 24231245
• 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 PMID 28235726

Identifiers

NCT: NCT06059261 · Lance

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗