Clinical trial NCT06059261: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Chongqing University Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Fujian Cancer Hospital
name: Sun Yat-sen University
First posted: 2023-09-28
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progress-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
measure: Recurrence-free survival(RFS)
timeFrame: 3 years
measure: Locoregional Relapse-Free Survival (LRFS)
timeFrame: 3 years
measure: Distant metastases-Free survival (DMFS)
timeFrame: 3 years
measure: Incidence rate of adverse events (AEs)
timeFrame: 3 years
measure: Compliance
timeFrame: 3 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
Study officials:
affiliation: Chongqing University Cancer Hospital
name: Jiang D Sui, Ph.D, M.D.
role: PRINCIPAL_INVESTIGATOR
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