Efficacy and Safety of Chidamide+Sintilimab+Bev as Second-Line Therapy in Advanced Extrapulmonary Neuroendocrine Carcinoma

Korábbi kezelés

• Prior exposure to any anti-angiogenic therapy or histone deacetylase (HDAC) inhibitor.
• Received any investigational drug within 4 weeks before the first dose of study treatment.
• Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, embolization, etc.) within 3 weeks before first dose.
• Received radiotherapy within 4 weeks before first dose.
• Residual radiation-related toxicity (e.g., pneumonitis, hepatitis, enteritis) from prior radiotherapy > 4 weeks before first dose, including symptomatic cases or those requiring corticosteroids.
• Received systemic immunosuppressive drugs within 4 weeks before first dose, except topical/inhaled corticosteroids or physiological systemic corticosteroids (≤ 10 mg/day prednisone equivalent).
• Received or plans to receive live attenuated vaccines within 4 weeks before first dose or during the study.
• Underwent major surgery within 4 weeks before first dose, or has unhealed wounds, ulcers, or fractures.
• Severe uncontrolled active infection, including hospitalization for infection within 4 weeks before first dose.
• Significant malnutrition requiring intravenous nutrition, unless corrected for > 4 weeks before first dose.
• Any arterial thromboembolic event (myocardial infarction, pulmonary embolism, unstable angina) within 6 months before enrollment.
• History of deep vein thrombosis or other severe thromboembolism within 3 months before enrollment (catheter-related or superficial vein thrombosis excluded).
• History of gastrointestinal perforation/fistula, peptic ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, intra-abdominal abscess, or chronic diarrhea within 6 months before enrollment; or intestinal stent placement.
• Any life-threatening bleeding event within 3 months before enrollment (requiring transfusion, surgery, or continuous treatment).
• Cerebrovascular accident (including transient ischemic attack) within 6 months before enrollment.
• Use of oral or parenteral anticoagulants or thrombolytics for 10 consecutive days within 10 days before first dose (prophylactic anticoagulation allowed).

Más betegség

• Active autoimmune disease requiring systemic therapy within 2 years before first dose; or primary immunodeficiency. Replacement therapy (e.g., thyroid hormone, insulin) is permitted.
• Active tuberculosis, or anti-tuberculosis treatment within 1 year before first dose.
• Interstitial lung disease requiring corticosteroid treatment.
• Active hepatitis B (HBsAg positive and HBV DNA ≥ 200 IU/mL) or active hepatitis C (HCV antibody positive and HCV RNA positive).
• Known HIV infection or syphilis.
• Symptomatic congestive heart failure (NYHA class II-IV), or symptomatic/uncontrolled arrhythmia.
• Uncontrolled arterial hypertension despite optimal treatment (systolic BP ≥ 150 mmHg or diastolic BP ≥ 100 mmHg).
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B or C cirrhosis.
• Uncontrolled metabolic disorders or other severe medical conditions that may increase study risk or confound result interpretation.
• Hereditary bleeding tendency or coagulation disorder.
• High bleeding risk per investigator assessment: severe esophageal/gastric varices, intermittent bleeding (e.g., hematochezia, hemoptysis).
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to any monoclonal antibody component or study drug excipients.
• History of alcoholism or drug abuse.

Laborértékek

• Resolved toxicity from prior anti-tumor therapy not recovered to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or non-clinically significant laboratory abnormalities).
• Use of aspirin (> 325 mg/day) or other platelet inhibitors for 10 consecutive days within 10 days before first dose.
• Any other acute or chronic disease, psychiatric disorder, or laboratory abnormality that, in the investigator's opinion, increases study risk or interferes with result interpretation.

Életkor

• History of other primary malignancy, except: Malignancy in complete remission for ≥ 2 years without treatment during study；adequately treated non-melanoma skin cancer or carcinoma in situ with no evidence of recurrence.

Egyéb

• Simultaneously participating in another interventional clinical study (observational or follow-up studies are allowed).
• Known symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Patients with treated and stable CNS metastases for ≥ 4 weeks and neurological symptoms recovered to grade ≤ 1 are allowed.
• Symptomatic or drainable pleural effusion, ascites, or pericardial effusion (only small asymptomatic effusions by imaging are allowed).
• Pregnant or breastfeeding female patients.

• Histologically or cytologically confirmed locally advanced, unresectable, or metastatic extrapulmonary neuroendocrine carcinoma (NEC).
• Failure of first-line standard systemic therapy, with documented disease progression during or after treatment by imaging or clinical evidence (e.g., cytology of new ascites or pleural effusion). Patients who discontinued first-line therapy due to intolerable toxicity are eligible.
• At least one measurable lesion per RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Able to provide written informed consent and comply with study visits and procedures.
• Age ≥ 18 years and ≤ 75 years.
• Life expectancy ≥ 12 weeks.
• Women of childbearing potential and men with female partners of childbearing potential must use effective contraception throughout the treatment period and for 6 months after the last dose of study treatment.
• Adequate organ and bone marrow function within 7 days before enrollment, without support treatments (blood products, growth factors, albumin) within 14 days before testing: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (HGB) ≥ 9.0 g/dL; serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); ALT/AST ≤ 3.0 × ULN (no liver metastasis) or ≤ 5.0 × ULN (with liver metastasis); serum albumin ≥ 25 g/L; serum creatinine (Cr) ≤ 1.5 × ULN; urine protein < 2+ or 24-hour urine protein < 1 g if urine protein ≥ 2+; INR ≤ 1.5 × ULN and APTT ≤ 1.5 × ULN.