Clinical Study Protocol for a Single-Center, Prospective, Single-Arm Trial Assessing Icaritin Soft Capsules as Postoperative Adjuvant Therapy in Hepatocellular Carcinoma Patients With High-Risk Factors for Recurrence
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Evaluation of Efficacy and Safety of Sintilimab Plus Bevacizumab and AG Regimen as First-Line Therapy in Patients with Surgically Ineligible Locally Advanced or Metastatic Cholangiocarcinoma
Objectives:
Primary Objective:
To assess the objective response rate (ORR) as per RECIST v1.1.
Secondary Objectives:
- To evaluate the disease control rate (DCR) per RECIST v1.1.
- To determine the duration of response (DOR) per RECIST v1.1.
- To measure progression-free survival (PFS) per RECIST v1.1.
- To characterize the safety profile.
- To determine overall survival (OS) .
Exploratory Objectives:
To investigate potential predictive biomarkers (e.g., PD-L1 expression, tumor mutational burden [TMB]) and their correlation with treatment efficacy (non-mandatory).
详细描述
This study is a single-arm, Phase II clinical trial evaluating the efficacy and safety of Sintilimab plus Bevacizumab and the AG regimen as first-line therapy in patients with surgically ineligible locally advanced or metastatic cholangiocarcinoma.
After providing informed consent, patients receive:
Sintilimab: 200 mg IV Q3W Bevacizumab: 15 mg/kg IV Q3W AG Chemotherapy: Nab-paclitaxel + Gemcitabine for 8 cycles.
Post-chemotherapy, patients continue Sintilimab + Bevacizumab maintenance until:
Disease progression Death Intolerable toxicity Withdrawal of consent Initiation of new antitumor therapy Other protocol-specified reasons (Maximum treatment duration: 24 months)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent prior to any trial-related procedures.
- •Male or female aged **≥18 years and ≤75 years**.
- •Histologically or cytologically confirmed, surgically unresectable locally advanced or metastatic cholangiocarcinoma.
- •No prior systemic therapy; subjects who completed postoperative adjuvant therapy **>6 months ago** are eligible.
- •Life expectancy >3 months.
- •At least one measurable lesion per RECIST 1.1 criteria.
- •ECOG PS score 0 or
- •Adequate organ function (all laboratory criteria below must be met):
- •（1）Absolute neutrophil count (ANC) **≥1.5×10⁹/L** without granulocyte colony-stimulating factor within 14 days; （2）Platelets **≥90×10⁹/L** without transfusion within 14 days; （3）Hemoglobin **>9 g/dL** without transfusion/recombinant erythropoietin within 14 days; （4）Total bilirubin ≤1.5×ULN; （5）AST/ALT ≤2.5×ULN (≤5×ULN allowed if liver metastases present); （6）Serum creatinine ≤1.5×ULN AND creatinine clearance (Cockcroft-Gault formula) **≥60 mL/min**; （7）INR or PT ≤1.5×ULN; （8）TSH within normal range; OR if abnormal, total T3 (or FT3) AND FT4 within normal limits; （9）Cardiac enzymes within normal limits (isolated abnormalities deemed clinically insignificant by investigator are allowed).
- •9. For women of childbearing potential:
- •（1）Negative urine/serum pregnancy test within 3 days before Cycle 1 Day 1 (confirm equivocal urine tests with serum testing).
- •（2）Non-childbearing potential defined as:
- •Postmenopausal (≥1 year amenorrhea), OR
- •Surgically sterilized/hysterectomy.
- •All subjects (regardless of gender) at conception risk must use contraception with <1% annual failure rate during treatment and for 120 days after last dose.
排除标准
- •Other malignancies within 5 years prior to first dose (excluding radically cured basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ).
- •Current participation in interventional clinical trials or receipt of other investigational drugs/devices within 4 weeks before first dose.
- •Prior therapy with:
- •Anti-PD-1/PD-L1/PD-L2 agents;
- •Drugs targeting stimulatory/co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
- •4. Systemic administration of antitumor Chinese herbal medicines or immunomodulators (e.g., thymosin, interferon, interleukin) within 2 weeks (except localized use for pleural effusion).
- •5. Active autoimmune disease requiring systemic treatment within 2 years (e.g., disease-modifying drugs, corticosteroids ≥10 mg/day prednisone equivalent, immunosuppressants).
- •Exclusions: Hormone replacement (thyroxine/insulin/physiologic steroids);
- •Known primary immunodeficiency;
- •Isolated autoantibody positivity requires investigator confirmation of no autoimmune disease.
- •6. Systemic glucocorticoids (excluding topical/inhaled) or immunosuppressive therapy within 4 weeks.Note: Physiologic-dose steroids (≤10 mg/day prednisone equivalent) permitted.
- •7. Prior anti-angiogenic therapy (e.g., bevacizumab).
- •Active bleeding within 3 months prior to first dose:
- •Hemoptysis (≥2.5 mL/fresh blood episode);
- •Gastrointestinal bleeding.
- •High bleeding risk: Tumor invasion of major vessels or radiologist/investigator-assessed bleeding tendency.
- •10. Major surgery within 4 weeks (excluding biopsy).
- •Severe unhealed wounds/ulcers/fractures.
- •Aspirin (>325 mg/day) or platelet-inhibiting NSAIDs for >10 consecutive days within 10 days prior to first dose.
- •13. Full-dose anticoagulants/thrombolytics for >10 consecutive days within 10 days prior to first dose.Note: Prophylactic low-dose anticoagulants allowed:
- •（1）Warfarin ≤1 mg/day (INR ≤1.5); （2）Heparin ≤12,000 U/day; （3）Aspirin ≤100 mg/day.
- •Hereditary bleeding disorders, coagulopathy, or thrombotic history.
- •Clinically uncontrolled pleural effusion/ascites (asymptomatic/minimal fluid without drainage allowed).
- •16. Allogeneic organ transplant (excluding corneas) or hematopoietic stem cell transplant.
- •17. Hypersensitivity to sintilimab/bevacizumab or excipients.
- •Inadequate recovery from prior intervention toxicities (i.e., >Grade 1 or not returned to baseline, excluding alopecia/fatigue).
- •19. HIV infection (HIV 1/2 antibody-positive).
- •Untreated active HBV:
- •HBsAg-positive AND HBV-DNA > local ULN;
- •Exceptions:
- •a. HBV-DNA <500 IU/mL with ongoing antiviral therapy; b. Anti-HBc (+) only with HBV-DNA monitoring.
- •Active HCV infection (HCV antibody-positive AND detectable HCV-RNA).
- •Live attenuated vaccines within 4 weeks prior to first dose.
- •Pregnancy or breastfeeding.
- •Uncontrolled systemic diseases, including:
- •Severe uncontrolled cardiac arrhythmias (e.g., complete LBBB, ≥Grade II AV block, VT/AF);
- •Unstable angina, CHF, NYHA Class ≥II heart failure;
- •Arterial thromboembolism within 6 months (e.g., MI, stroke, TIA);
- •Major surgery/unhealed wounds within 4 weeks; biopsy within 7 days (except IV catheterization);
- •Uncontrolled hypertension (>140/90 mmHg);
- •Active tuberculosis;
- •Uncontrolled systemic infection;
- •Clinical diverticulitis, intra-abdominal abscess, GI obstruction;
- •Decompensated liver disease/active hepatitis;
- •Uncontrolled diabetes (fasting glucose >10 mmol/L);
- •Urine protein ≥++ AND 24-hr urine protein >1.0 g.
- •Psychiatric disorders impairing treatment compliance.
- •Any condition that may:
- •（1）Interfere with trial results; （2）Prevent full study participation; （3）Pose additional risks (per investigator judgment).
研究组 & 干预措施
Study Cohort
干预措施: Sintilimab combined with bevacizumab and albumin-bound paclitaxel plus gemcitabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From baseline (within 28 days prior to enrollment) through disease progression or study completion, up to approximately 2 years.
Tumor assessments are based on RECIST 1.1. Imaging modalities for this evaluation require: Mandatory scans (each cycle): Contrast-enhanced CT or MRI of the chest and abdomen Baseline assessments (within 28 days ): Contrast-enhanced CT/MRI of the pelvis Brain MRI Whole-body bone scan Additional baseline imaging if clinically indicated: Contrast-enhanced neck CT (if cervical lymphadenopathy present) PET/CT protocol: Acceptable for baseline screening only Any abnormal findings must undergo confirmatory anatomical imaging (CT/MRI) for target lesion designation
次要结局
未报告次要终点