Nasopharyngeal Carcinoma
Conditions
Keywords
Nasopharyngeal Carcinoma
Brief summary
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
DRUGEnvafolimab 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 administered by intravenous infusion on day 1 of each cycle at 100mg/m2 every 3 weeks for 2 cycles. Adjuvant treatment Phase: Envafolimab was administered on day 1 every 3 weeks at 300 mg for 8 cycles as a subcutaneous injection. Intensity-modulated radiotherapy: 69.96Gy/33fractions/7 weeks,5 fractions/week, 1 fraction/day.
Sponsors
Chongqing University Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) after Induction Therapy | From enrollment to the end of induction therapy at 12 weeks | The proportion of patients in whom all target and non-target lesions confirmed at baseline have completely disappeared, as assessed by magnetic resonance imaging (MRI) following the completion of induction therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) after Induction Therapy | From enrollment to the end of induction therapy at 12 weeks | The proportion of patients who achieve an objective reduction in tumor size after induction therapy, including those with complete response and partial response. |
| Progression Free Survival (PFS) | 2 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. |
| Overall survival (OS) | 2 years | Overall survival is measured from randomization until death due to any cause or the latest known date alive. |
| Locoregional Relapse-Free Survival (LRRFS) | 2 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. |
| Distant metastases-Free survival (DMFS) | 2 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) | through study completion, an average of 1 year | 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. |
Countries
China
Contacts
CONTACTXin Zhang, Ph.D, M.D.
CONTACTJiang D Sui, Ph.D, M.D.
PRINCIPAL_INVESTIGATORJiang D Sui, Ph.D, M.D.
Chongqing University Cancer Hospital
Outcome results
None listed