A Multi-cohort Exploratory Study to Evaluate the Efficacy and Safety of Albumin-bound Paclitaxel (Ⅱ)-Combined Regimens for Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This is a prospective, multi-center, multi-cohort exploratory study. Cohort 1 enrolls 39 patients with unresectable locally advanced or metastatic pancreatic cancer, who will receive first-line treatment with cisplatin plus nab-paclitaxel (Ⅱ), capecitabine, and gemcitabine (PAXG).
Cohort 2 enrolls 27 patients with borderline-resectable or high-risk resectable pancreatic cancer, who will receive neoadjuvant therapy with the PAXG regimen.
Cohort 3 enrolls patients with pancreatic cancer who have undergone curative resection, who will receive adjuvant therapy with nab-paclitaxel (Ⅱ), capecitabine, and gemcitabine.
Objectives of Study: To evaluate the efficacy and safety of nab-paclitaxel (Ⅱ)-based regimes for pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Aged 18 to 75 years old.
- •Histopathologically confirmed pancreatic adenocarcinoma meeting any one of the following conditions: (1) Unresectable locally advanced or metastatic pancreatic cancer, with no prior systemic anti-tumor therapy for advanced disease. Prior neoadjuvant/adjuvant chemotherapy is permitted, provided the interval from completion of prior chemotherapy to study drug administration is more than 6 months. (2) High-risk resectable or borderline resectable pancreatic cancer assessed by a multidisciplinary team.(3) Curative resection (R0 or R1 resection) performed without prior neoadjuvant therapy, and adjuvant treatment can be initiated within 12 weeks postoperatively.
- •Presence of at least one measurable lesion per RECIST v1.1 (exclusive to participants in Cohort 3).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Estimated survival time ≥ 3 months.
- •Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5×10⁹/L, platelet count (PLT) ≥ 100×10⁹/L, hemoglobin (Hb) ≥ 90 g/L.
- •Adequate liver function: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×ULN (≤5×ULN allowed in patients with liver metastases); total bilirubin ≤ 1.5×ULN.
- •Adequate renal function: serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min (calculated by Cockroft-Gault formula).
- •Adequate coagulation function: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
- •Women of childbearing potential must have a negative serum/urine pregnancy test within 14 days prior to enrollment, be non-lactating, and agree to use effective contraception throughout the study and for 6 months after the last study treatment. Male participants must agree to effective contraception during the study and for 6 months after study completion.
- •Able to understand the study information; participant or legal representative voluntarily provides written informed consent.
排除标准
- •History of other malignant tumors within the past 5 years
- •Known hypersensitivity or intolerance to any study drug or excipients.
- •Confirmed homozygous or compound heterozygous DPYD variants leading to complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Presence of any of the following comorbidities: ① Severe or uncontrolled cardiovascular disease: New York Heart Association (NYHA) Class II or higher chronic heart failure, uncontrolled hypertension (systolic BP >150 mmHg and/or diastolic BP >90 mmHg despite stable medication), etc. ② Severe respiratory disorders: asthma requiring inhaled/systemic glucocorticoids, active chronic obstructive pulmonary disease, etc. ③ Confirmed neurological diseases (epilepsy, dementia, etc.) or Grade ≥2 peripheral sensory/motor neuropathy. ④ Uncontrolled diabetes mellitus (fasting blood glucose ≥10 mmol/L under stable treatment). ⑤ Severe chronic or active infections requiring ≥1 consecutive week of systemic antibacterial, antifungal or antiviral therapy (including tuberculosis). ⑥ Active HIV infection (HIV antibody positive); untreated active HBV (HBsAg/HBcAg positive with HBV-DNA above institutional upper limit of normal) or active HCV infection (HCV antibody positive with HCV-RNA above institutional upper limit of normal).
- •Untreated active brain metastases (including symptomatic brain or leptomeningeal metastases). Participants with brain metastases are eligible only if brain lesions are stable on imaging performed ≥4 weeks prior to first study dose, no new neurological symptoms or baseline symptom relapse, and no systemic steroid administration for ≥14 days before study treatment initiation, with no evidence of new or enlarged metastatic lesions.
- •Medical history as follows: ① Major abdominal/thoracic surgery within 28 days prior to first study dose, or planned major surgery during the study period (diagnostic puncture and infusion port implantation excluded). ② Severe cardiovascular/cerebrovascular events (myocardial infarction, unstable angina, cerebrovascular accident) within 6 months prior to enrollment; clinically silent lacunar infarcts are permitted.
- •History of deep vein thrombosis or pulmonary embolism within 3 months prior to enrollment.
- •Inability to swallow or untreated malabsorption syndrome.
- •Receipt of any investigational product within 1 month prior to enrollment.
- •Any other condition judged by the investigator to render the participant unsuitable for study participation.
研究组 & 干预措施
Chort 1
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, Treatment will continue until disease progression or intolerable toxicity.
干预措施: Gemcitabine (Drug)
Chort 1
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, Treatment will continue until disease progression or intolerable toxicity.
干预措施: Albumin-bound Paclitaxel (Ⅱ) (Drug)
Chort 2
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, with a maximum of 12 treatment cycles.
干预措施: Albumin-bound Paclitaxel (Ⅱ) (Drug)
Chort 3
Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q3w, for a total treatment duration of up to 6 months.
干预措施: Albumin-bound Paclitaxel (Ⅱ) (Drug)
Chort 1
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, Treatment will continue until disease progression or intolerable toxicity.
干预措施: Cisplatin (Drug)
Chort 2
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, with a maximum of 12 treatment cycles.
干预措施: Cisplatin (Drug)
Chort 1
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, Treatment will continue until disease progression or intolerable toxicity.
干预措施: Capecitabine (Drug)
Chort 2
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, with a maximum of 12 treatment cycles.
干预措施: Gemcitabine (Drug)
Chort 2
Cisplatin + Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q2w, with a maximum of 12 treatment cycles.
干预措施: Capecitabine (Drug)
Chort 3
Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q3w, for a total treatment duration of up to 6 months.
干预措施: Capecitabine (Drug)
Chort 3
Albumin-bound Paclitaxel (Ⅱ) + Capecitabine + Gemcitabine, q3w, for a total treatment duration of up to 6 months.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: After all participants in each dose cohort complete the 21-day DLT observation period.
Disease-Free Survival (DFS)
时间窗: From informed consent signature to tumor recurrence or all-cause death (whichever occurs first), assessed up to 20 months.
Progression-Free Survival (PFS)
时间窗: Time from subject's first study drug administration to first documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, assessed up to 5.5 months.
1-Year Event-Free Survival Rate (1y-EFS Rate)
时间窗: 12 months after signing informed consent, until first EFS event or loss to follow-up.
次要结局
- Objective Response Rate (ORR)(Tumor response assessment every 8 weeks (±7 days) after first study drug administration until disease progression, death or end-of-follow-up, assessed up to 5.5 months.)
- Maximum Tolerated Dose (MTD)(After DLT observation completion and RP2D determination for all dose cohorts, assessed up to 1 months.)
- R0 Resection Rate(After neoadjuvant therapy completion, at pathological report of surgical specimen, assessed up to 7 months.)
- Incidence of Adverse Events(From the time of informed consent signature through 30 days after last study drug administration.)
- Disease Control Rate (DCR)(Tumor response assessment every 8 weeks (±7 days) after first study drug administration until disease progression, death or end-of-follow-up, assessed up to 5.5 months..)
- Overall Survival (OS)(Time from subject's first study drug administration to death from any cause, assessed up to 40 months.)
- Dose-Limiting Toxicity (DLT)(After all participants in each dose cohort complete the 21-day DLT observation period.)
- Event-Free Survival (EFS)(From informed consent signature to first local recurrence, distant metastasis, tumor progression, second malignancy or all-cause death (whichever occurs first), assessed up to 16 months.)
- Major Pathological Response (MPR) Rate(Upon completion of pathological diagnosis of resected surgical specimen, assessed up to 7 months.)
- Pathological Complete Response (pCR) Rate(Upon completion of pathological diagnosis of resected surgical specimen, assessed up to 7 months.)
- Duration of Response (DOR)(Time from first documented CR or PR to subsequent disease progression or death from any cause, whichever occurs first, until end-of-follow-up, assessed up to 6 months.)