A Phase II Randomized Study of Gemcitabine and Nab-paclitaxel in Combination With S- 1/LV (GASL) or Oxaliplatin (GAP) as First-line Treatment for Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 66
- 试验地点
- 4
- 主要终点
- Best objective response rate (ORR)
研究概览
简要总结
Gemcitabine and nab-paclitaxel are one standard of care for metastatic pancreatic adenocarcinoma (mPDAC) but the progression free survival (PFS) of the regimen is only 5.5 months. Previous phase II study showed gemcitabine and nab-paclitaxel plus cisplatin had a PFS of 10.1 months in mPDAC. This study will evaluate the efficacy and safety of gemcitabine, nab-paclitaxel plus S-1/LV (GASL) against gemcitabine, nab-paclitaxel plus oxaliplatin (GAP) in patients with mPDAC.
详细描述
Gemcitabine and nab-paclitaxel are one standard of care for metastatic pancreatic adenocarcinoma (mPDAC) but the progression free survival (PFS) of the regimen is only 5.5 months. Previous phase II study showed gemcitabine and nab-paclitaxel plus cisplatin had a PFS of 10.1 months in mPDAC. However, the nephrotoxicity of cisplatin is always a concern therefore cisplatin was substituted with oxaliplatin in current study. S-1 monotherapy has shown promising anti-tumor activity against PDAC with a manageable safety profile which provided the opportunity of combination with other agents. In this study, we will evaluate the efficacy and safety of gemcitabine, nab-paclitaxel plus S-1/LV (GASL) against gemcitabine, nab-paclitaxel plus oxaliplatin (GAP) in patients with mPDAC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A.Cytology or histology confirmed pancreatic adenocarcinoma with evidence of distant metastasis.Mixed component of other cell type (eg, adenosquamous, adenocarcinoma with neuroendocrine differentiation) is eligible but should notify PI before registration.
- •B.No history of prior chemotherapy for pancreatic cancer, except adjuvant chemotherapy that completed at least 6 months before documentation of recurrence by imaging study.
- •C.Patients with prior radiotherapy are eligible if there are other measurable target lesions that is not irradiated.
- •D.At least one measurable lesion according to RECIST version 1.1
- •E.Ability to understand and willingness to sign a written informed consent document.
- •F.ECOG performance status 0-1
- •G.Age of 20 years or above
- •H.Adequate organ function as defined by the following criteria:
- •absolute neutrophil count (ANC) ≥ 1,500/mm3 hemoglobin level ≥ 9 g/dL platelet count ≥ 100,000/mm3 total bilirubin ≤ 2 ULN or ≤5 ULN if caused by biliary obstruction and achieving adequate drainage judged by investigator aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5.0×ULN in the presence of liver metastases creatinine clearance rate (CCr) ≥ 50 mL/min (24-hour urine collection or calculated by Cockroft-Gault formula; male: [(140 - age) × weight (kg)]/[72 × serum creatinine(mg/dL)];female=male x 0.85
- •I.Patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study.
排除标准
- •A. Other malignancy within the past 5 years except for adequately treated localized cancer or carcinoma in situ;All patients with other malignancy within the past 5 years should notify PI before registration.
- •B.Active or uncontrolled infection;
- •C.Significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications at physician discretion
- •D.Pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential.
- •E.History of active autoimmune disease within 3 years or use of steroid more than prednisolone 10mg/day.
研究组 & 干预措施
GASL arm
eligible patients will receive gemcitabine 800 mg/m2 on day 1, nab-paclitaxel 125 mg/m2 on day 1, S-1 orally 60-100 mg/day [depending on patient's baseline body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows:
- BSA < 1.25 m2: 60 mg/day
- 1.25 m2 ≤ BSA < 1.5 m2: 80 mg/day
- BSA ≥ 1.5 m2: 100 mg/day
干预措施: leucovorin (Drug)
GAP arm
eligible patients will receive gemcitabine 800 mg/m2, nab-paclitaxel 125 mg/m2 and oxaliplatin 75mg/m2 on day 1 in a 2-week cycle.
干预措施: Oxaliplatin (Drug)
GASL arm
eligible patients will receive gemcitabine 800 mg/m2 on day 1, nab-paclitaxel 125 mg/m2 on day 1, S-1 orally 60-100 mg/day [depending on patient's baseline body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows:
- BSA < 1.25 m2: 60 mg/day
- 1.25 m2 ≤ BSA < 1.5 m2: 80 mg/day
- BSA ≥ 1.5 m2: 100 mg/day
干预措施: Gemcitabine 1000 mg (Drug)
GAP arm
eligible patients will receive gemcitabine 800 mg/m2, nab-paclitaxel 125 mg/m2 and oxaliplatin 75mg/m2 on day 1 in a 2-week cycle.
干预措施: Nab paclitaxel (Drug)
GAP arm
eligible patients will receive gemcitabine 800 mg/m2, nab-paclitaxel 125 mg/m2 and oxaliplatin 75mg/m2 on day 1 in a 2-week cycle.
干预措施: Gemcitabine 1000 mg (Drug)
GASL arm
eligible patients will receive gemcitabine 800 mg/m2 on day 1, nab-paclitaxel 125 mg/m2 on day 1, S-1 orally 60-100 mg/day [depending on patient's baseline body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows:
- BSA < 1.25 m2: 60 mg/day
- 1.25 m2 ≤ BSA < 1.5 m2: 80 mg/day
- BSA ≥ 1.5 m2: 100 mg/day
干预措施: Nab paclitaxel (Drug)
GASL arm
eligible patients will receive gemcitabine 800 mg/m2 on day 1, nab-paclitaxel 125 mg/m2 on day 1, S-1 orally 60-100 mg/day [depending on patient's baseline body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows:
- BSA < 1.25 m2: 60 mg/day
- 1.25 m2 ≤ BSA < 1.5 m2: 80 mg/day
- BSA ≥ 1.5 m2: 100 mg/day
干预措施: S1 (Drug)
结局指标
主要结局
Best objective response rate (ORR)
时间窗: 6 years
tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.
次要结局
- Disease control rate (DCR)(6 years)
- Progression-free survival (PFS)(6 years)
- Overall survival (OS)(6 years)
- Duration of response (DOR)(6 years)
- Incidence of Treatment-related Adverse Events [Safety and Tolerability](6 years)