A Phase III, Multi-center, Randomized, Controlled Study to Compare the Efficacy and Safety of Gemcitabine Alone vs. ON 01910.Na Combined With Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 46
- 主要终点
- Survival
研究概览
简要总结
The question being asked in this study is: Will patients with advanced pancreatic cancer live significantly longer if they are treated with a combination of Gemcitabine and ON 01910.Na than if they are treated with Gemcitabine alone? There are two parts to this study. In the first part of the study, patients with metastatic pancreatic cancer who have received no prior chemotherapy for this disease will be assigned by chance either to the group that will be treated with both Gemcitabine and ON 01910.Na (about 100 patients will be in this group) or, to the group that will be treated with Gemcitabine only (about 50 patients will be in this group). How long patients survive in the 2 groups will be compared. If it looks like there is no difference between the groups, the study will stop. If it looks like patients in the group that were treated with both Gemcitabine and ON 01910.Na survive longer, the study will continue into a second part where more patients will be treated in order to confirm and better understand the findings of the first part of the study.
详细描述
This will be a Phase III study with sample size recalculation after 100 events have occurred. The study will be open-label, randomized, controlled, multi-center and will be conducted at approximately 200 to 300 study sites (60 to 80 study sites in the first portion of the trial).
In the first portion of the study, a total of 150 patients with metastatic pancreatic cancer who have received no prior chemotherapy for this disease will be randomized in a 2:1 fashion to 1 of the 2 following treatment regimens:
- Arm A: Gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4 week cycle + ON 01910.Na 1800 mg/m2 via 2 hr continuous intravenous infusion (CIV) infusions administered twice weekly for 3 weeks of a 4 week cycle (approximately 100 patients)
- Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle (approximately 50 patients).
Patients will be stratified at entry using the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG scores of 0 1 vs. ECOG scores of 2; patients with higher scores will not be enrolled).
Patients will remain on study until disease progression or death from any cause, whichever comes first. Moreover, after treatment discontinuation for any cause, all patients will be followed until death.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients at least 18 years old presenting with histopathologically or cytologically confirmed metastatic adenocarcinoma of the pancreas; metastatic disease is defined as disease which has spread beyond the peri-pancreatic lymph nodes.
- •Patients must have received no prior chemotherapy for pancreatic cancer, including adjuvant chemotherapy.
- •Measurable disease, defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) ≥20 mm using conventional techniques or ≥10 mm with spiral computed tomography (CT) scan; measurable lymph nodes must be ≥15 mm in the short axis.
- •ECOG Performance Status of 0, 1, or
- •Patients must have adequate renal function and serum creatinine ≤2.0 mg/dL.
- •Patients must have adequate liver function as defined by total bilirubin ≤2.0 mg/dL and transaminase levels no higher than 3.0 times the institution's upper limit of normal (ULN). Patients with hepatic metastases may have transaminase levels of up to 5.0 times the ULN.
- •All patients must have a serum albumin ≥3.0 g/dL.
- •Patients must have adequate bone marrow (BM) function as defined by a granulocyte count ≥1,500/mm3, a platelet count ≥100,000/mm3, and hemoglobin >9 g/dL.
- •Disease-free period of more than 5 years from prior malignancies other than pancreas (except curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix and ductal carcinoma in situ [DCIS] breast disease).
- •Adequate contraceptive regimen (including prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study for female patients of reproductive potential or female partners of male patients.
- •Female patient with reproductive potential must have a negative urine beta human chorionic gonadotropin (bHCG) pregnancy test at Screening.
- •Willing to adhere to the prohibitions and restrictions specified in this protocol.
- •Patient must have signed an informed consent document.
排除标准
- •Patients with unresectable locally advanced disease without evidence of disease elsewhere.
- •Life expectancy of less than 12 weeks.
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or seizure disorder.
- •Active infection not adequately responding to appropriate therapy.
- •Symptomatic or clinically evident ascites.
- •Serum sodium less than 130 mEq/L or conditions that may predispose patients to hyponatremia.
- •Female patients who are pregnant or lactating.
- •Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol.
- •Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
- •Evidence of brain metastases.
- •Any concurrent administration and/or prior administration within 4 weeks of the first dose of study drug, of radiotherapy, or immunotherapy.
- •Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements, or inability to comply with study and/or follow-up procedures (e.g., drug addition, chronic non-compliance, etc.).
研究组 & 干预措施
Arm A: Combination
Arm A: Gemcitabine, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle, + ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle.
干预措施: ON 01910.Na (Drug)
Arm A: Combination
Arm A: Gemcitabine, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle, + ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle.
干预措施: Gemcitabine (Drug)
Arm B: Gemcitabine only
Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Survival
时间窗: 18 months
This study's primary outcome is overall survival, defined as the time from randomization to death from any cause. All patients will be followed until death. Patients lost to follow-up will be censored at the time last known alive.
次要结局
- Population Pharmacokinetics(18 months)
- Full Pharmacokinetics(18 Months)
- Safety/tolerability(18 months)
- QOL questionnaire(18 months)
- Progression-free survival(18 months)
- Tumor size(18 months)
- Biomarkers(18 months)