An Open, Randomised, Clinical Phase II Trial in Patients With Unresectable Advanced Pancreatic Cancer Investigating the Efficacy, Safety, and Pharmacokinetics of BI 2536 Administered in Repeated 3-week Cycles as a Single i.v. Dose of 200 mg on Day 1 or as 60 mg Doses on Days 1, 2, and 3
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 10
- 主要终点
- Best Objective Response Evaluated According to the RECIST Criteria by Independent Review
研究概览
简要总结
The trial is conducted in order to evaluate the efficacy, safety and pharmacokinetics of BI 2536 in the treatment of unresectable advanced pancreatic cancer as first line or second line therapy. A secondary aim is to identify the most suitable dosage regimen for the further phase II and III clinical programme of BI 2536. To achieve this objective, two dosage regimens are compared in patients receiving first line therapy.
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
- •male or female patient aged 18 years or older
- •patient with confirmed diagnosis of unresectable, either locally advanced or metastatic, ductal adenocarcinoma of the pancreas
- •patient who is either chemonaïve (for the first line cohorts), or who presents with progressive disease under first line chemotherapy with a gemcitabine based regimen (for the second line cohort)
- •Karnofsky performance status of ¿ 70% for the first line cohorts, and Karnofsky performance status ¿ 50% for the second line cohort
- •patient with at least one measurable tumour lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension (longest diameter to be recorded)
- •life expectancy of at least three months
- •patient must have given written informed consent consistent with the guidelines of the international conference on harmonisation for good clinical practice (ICH-GCP) as well as with local legislation
排除标准
- •prior adjuvant chemotherapy (for first line cohorts only)
- •ampullary carcinoma of the pancreas
- •hypersensitivity to the trial drug or the excipients
- •persistence of toxicities of prior anti cancer therapies which are deemed to be clinically relevant
- •known second malignancy requiring therapy
- •brain metastases which are symptomatic or require therapy
- •absolute neutrophil count less than 1.500/mm3
- •platelet count less than 100.000/mm3
- •haemoglobin less than 9 mg/dl
- •aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2.5 times the upper limit of normal, or AST or ALT greater than 5 times the upper limit of normal in case of known liver metastases
- •bilirubin greater than 3.0 mg/dl (> 52 ¿mol/l, SI unit equivalent) under adequate drainaging measures (in case of obstructive jaundice)
- •serum creatinine greater than 2.0 mg/dl
- •concomitant intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug
- •radiotherapy within the past four weeks prior to treatment with the trial drug
- •hormone- or immunotherapy or therapy with a biologic response modifier within the past four weeks
- •treatment with any other investigational drug within the past four weeks
- •men or women who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. abstinence, condom with spermicidal coating, diaphragm with spermicidal coating, oral contraceptive, progesterone implant, sterilisation) during the trial
- •pregnancy or lactation
- •patients unable to comply with the protocol
研究组 & 干预措施
BI 2536 Low dose
Day 1 - 3
干预措施: BI 2536 (Drug)
BI 2536 High dose
Day 1
干预措施: BI 2536 (Drug)
结局指标
主要结局
Best Objective Response Evaluated According to the RECIST Criteria by Independent Review
时间窗: Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.
Best objective response: Tumour assessment by independent review of tumour imaging by an external contract research organization (CRO) according to Response Evaluation Criteria In Solid Tumours (RECIST) after every second treatment course, including imaging (e.g. Computed tomography (CT), Magnetic resonance imaging (MRI)) and submission of image(s) to central imaging unit. Complete remission (CR): Disappearance of all target lesions for at least 4 weeks from the documentation of CR. Partial remission (PR): At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum Longest Diameter (LD). Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as references the smallest sum LD since the treatment started. No best response: includes all RECIST categories which are considered as failing to respond to therapy, e.g. progressive disease, death or unknown.
次要结局
- Tumour Control After the Fourth Treatment Course(Tumour measurements performed at screening (day -21 to -1) and at the end of of the fourth 3-week treatment cycle, up to 105 days.)
- Duration of Overall Response(Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.)
- Progression Free Survival (PFS)(Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.)
- Overall Survival (OS)(From first treatment till the end of the trial or when a patient concluded the trial, up to 336 days.)
- Best Objective Response Evaluated According to the RECIST Criteria by Investigator Assessment(Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.)
- One-year Survival(1 year, see description for detailed definition of the time frame.)
- Number of Participants With Carbohydrate Antigen 19-9 (CA19-9) Response(Blood samples for CA19-9 analysis were collected on Days 1, 2, and 5 of each treatment period, up to 357 days.)
- Number of Participants With Dose Limiting Toxicity (DLT)(Tumour measurements performed at screening (day -21 to -1), at the end of every other treatment period (2x 3 weeks), and at the end of the trial or when a patient concluded the trial, up to 357 days.)
- Quality of Life Assessment, Including Clinical Benefit Response: Overall Health(Data from the last available questionnaire for each patient. Questionnaires were taken at screening (day -21 to -1), at the beginning (Day 1) and end (Day 22 ± 3) of every treatment period (3 weeks), and at the end of the trial, up to 357 days.)
- Quality of Life Assessment, Including Clinical Benefit Response: Quality of Life(Data from the last available questionnaire for each patient. Questionnaires were taken at screening (day -21 to -1), at the beginning (Day 1) and end (Day 22 ± 3) of every treatment period (3 weeks), and at the end of the trial, up to 357 days.)
- Number of Participants With Incidence and Intensity of Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE)(From first administration until 21 days after the day of last administration, up to 16 cycles, up to 357 days.)