A Randomized Controlled, Open Label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1+GEM vs GEM Alone in Patients With Measurable Locally Advanced/Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 218
- 试验地点
- 68
- 主要终点
- Overall Survival
研究概览
简要总结
The aim of this adaptive Phase 3 trial is to show a statistically significant superiority of EndoTAG-1 in combination with gemcitabine compared to gemcitabine monotherapy in patients with locally advanced/metastatic pancreatic cancer after FOLFIRINOX failure.
详细描述
The objective of the study was to assess the safety and efficacy of a combination therapy of EndoTAG-1 plus gemcitabine vs. gemcitabine monotherapy in patients with locally advanced and/or metastatic adenocarcinoma of the pancreas eligible for second-line therapy after failing first line therapy with FOLFIRINOX
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
- •Age ≥ 18 years
- •Written informed consent
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas
- •Metastatic or locally advanced disease that is considered unresectable
- •Measurable / assessable disease according to RECIST v.1.1
- •Documented disease progression on first line FOLFIRINOX
- •Negative pregnancy test
- •Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential during the course of the study and for 90 days after last treatment (excluding women who are not of childbearing potential and men who have been sterilized).
- •ECOG performance status 0 or 1
排除标准
- •Cardiovascular disease, New York Heart Association (NYHA) III or IV
- •History of severe supraventricular or ventricular arrhythmia
- •History of coagulation or bleeding disorder
- •History of acute myocardial infarction within 6 months before randomization
- •History of congestive heart failure
- •Acute or chronic inflammation (autoimmune or infectious)
- •Significant active/unstable non-malignant disease likely to interfere with study assessments
- •Laboratory tests (hematology, chemistry) outside specified limits:
- •WBC ≤ 3 x 10³/mm³
- •ANC ≤ 1.5 x 10³/mm³
- •Platelets ≤ 100.000/mm³
- •Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)
- •aPTT > 1.5 x ULN
- •Serum creatinine > 2.0 mg/dl (> 176.8 μmol/l)
- •AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN
- •Alkaline phosphatase > 2.5 x ULN
- •Total bilirubin > 2 x ULN
- •Albumin < 2.5 g/dL
- •Clinically significant ascites
- •Any anti-tumor treatment (except FOLFIRINOX as the first-line therapy) for pancreatic adenocarcinoma before enrollment. Note: Patients who have undergone surgical interventions for pancreatic adenocarcinoma will be eligible.
- •Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field
- •Major surgery < 4 weeks prior to enrollment
- •Pregnant or nursing
- •Investigational medicinal product < 4 weeks of enrollment
- •Documented HIV history
- •Active hepatitis B infection requiring acute therapy Note: Subjects infected by the hepatitis B virus will be eligible for the study if they have no signs of hepatic decompensation and meet the liver function tests eligibility criteria.
- •Known hypersensitivity to any component of the EndoTAG-1 and/or gemcitabine formulations
- •History of malignancy other than pancreatic cancer < 3 years prior to enrollment, except nonmelanoma skin cancer or carcinoma in situ of the cervix treated locally
- •Vulnerable populations (e.g. subjects unable to understand and give voluntary informed consent)
研究组 & 干预措施
EndoTAG-1 and Gemcitabine
EndoTAG-1 22 mg/m² twice weekly plus Gemcitabine 1000mg/m² once weekly for 1 cycle (8 weeks) consisting of 3 weeks of treatment and 1 week rest followed by 3 weeks of treatment and 1 week rest until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent.
干预措施: EndoTAG-1 (Drug)
EndoTAG-1 and Gemcitabine
EndoTAG-1 22 mg/m² twice weekly plus Gemcitabine 1000mg/m² once weekly for 1 cycle (8 weeks) consisting of 3 weeks of treatment and 1 week rest followed by 3 weeks of treatment and 1 week rest until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent.
干预措施: Gemcitabine (Drug)
Gemcitabine Monotherapy
Gemcitabine 1000mg/m² once weekly, for 1 cycle (8 weeks) consisting of 3 weeks of treatment and 1 week rest followed by 3 weeks of treatment and 1 week rest until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization to death from any cause or last day known to be alive, up to approximately 33.5 months (assessed continuously during treatment)
The efficacy of EndoTAG-1 treatment was demonstrated through number of events, meaning subject death, compared to number of subjects censored at the time of analysis.
次要结局
- Progression Free Survival (PFS)(From randomization to either first observation of progressive disease or occurrence of death, up to approximately 33.5 months (assessed continuously during treatment))
- Percentage of Subjects With Objective Response(Up to approximately 33.5 months (assessed continuously during treatment))
- Duration of Response(From the first documentation of objective tumor response (date of the first CR or PR) to objective tumor progression or death due to any cause.)
- Percentage of Subjects With Disease Control According to RECIST v.1.1(Up to approximately 33.5 months (assessed continuously during treatment))
- Serum Carcinoma Antigen 19-9 (CA 19-9) Response Rate(Up to approximately 33.5 months (assessed at baseline, end of cycle 1 or the full treatment course))