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

Phase 2

Recruiting

• Conditions: Nasopharyngeal Carcinoma
• Interventions: Drug: Envafolimab and recombinant human endostatin combined with chemoradiotherapy

• Registration Number: NCT06059261
• Lead Sponsor: Chongqing University Cancer Hospital

Brief Summary

This is a multicenter, 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 multicenter, 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.

Study Timeline

• Study First Submitted: 2023-09-23
• Study First Submitted QC: 2023-09-23
• Study First Posted: 2023-09-28
• Status Verified: 2024-08
• Study Start: 2024-08-04
• Last Update Submitted: 2024-08-04
• Last Update Posted: 2024-08-06
• Primary Completion: 2027-10-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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. 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.
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Envafolimab and recombinant human endostatin combined with chemoradiotherapy	Envafolimab and recombinant human endostatin combined with chemoradiotherapy	Intervention Description: Induction envafolimab combined with recombinant endostatin and gemcitabine and cisplatin therapy for three cycles (every 3 weeks) followed by definitive radiotherapy with concurrent cisplatin chemotherapy. After 4 weeks of the completion of radiotherapy, adjuvant envafolimab therapy will begin every 3 weeks for 8 cycles or continue until progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progress-free survival (PFS)	3 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	3 years	Overall survival is measured from randomization until death due to any cause or the latest known date alive.
Locoregional Relapse-Free Survival (LRFS)	3 years	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.
Recurrence-free survival(RFS)	3 years	Defined as the time from randomization to documented disease recurrence (distant metastasis or local disease recurrence) or death from any cause, whichever occurs first.
Distant metastases-Free survival (DMFS)	3 years	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.
Incidence rate of adverse events (AEs)	3 years	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.
Compliance	3 years	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.

Trial Locations

Locations (1)

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China