Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-centre, Sequential Phase Ib/IIa Study
试验速览
- 阶段
- 1 期
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Determine the safety profile and the maximum tolerated dose (MTD) of AXP107-11 alone and when given in combination with gemcitabine standard therapy.
研究概览
简要总结
The purpose of this study is to assess the effect and safety of AXP107-11 alone, and in combination with gemcitabine standard therapy, in patients with advanced or metastatic cancer of the pancreas. The safety, pharmacokinetics and efficacy of AXP107-11 in these patients will also be studied.
详细描述
The annual incidence rate of pancreatic cancer is almost identical to the mortality rate. Despite a low incidence rate, pancreatic cancer is the fourth leading cause of cancer mortality in both men and women. Today is the only potentially curative option of these patients complete surgical resection. However, a majority of the patients (up to 80%) are not eligible for surgery for different reasons.
Today is gemcitabine the accepted first-line treatment for these patients. Recent advances in the management of pancreatic cancer suggest that gemcitabine may be improved by combining it with other anticancer drugs.
One attractive therapeutic option is genistein. Genistein appears to sensitize tumors to chemotherapy both by targeting the tumor cells and also by targeting components of the tumor microenvironment.
However, the limited bioavailability of genistein in its known crystalline form has led to difficulties in attaining adequate plasma concentration, resulting in limited application and dissemination in the clinical setting. To overcome this limitation, a novel crystalline form of genistein with improved pharmaceutical properties is being used. AXP107-11, a crystalline salt of genistein has improved physiochemical properties (solubility, dissolution rate, bioavailability) as compared to the known crystalline form of genistein.
In this study, AXP107-11, will be investigated alone and in combination with gemcitabine in patients with pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 at the time of signing the informed consent
- •Histologically confirmed adenocarcinoma of the pancreas
- •Metastatic or locally advanced, unresectable disease stage III-IV.
- •Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions
- •Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4).
- •Life expectancy of more than three months
- •Negative pregnancy test for female patients
- •For fertile women, willingness to perform double-barrier contraception during study and for four weeks after last treatment
- •Able and willing to sign the informed consent form
排除标准
- •Previous or ongoing severe supraventricular or ventricular arrhythmia
- •Previous or ongoing coagulation or bleeding disorder (PTT > 1.5 x ULN)
- •HIV infection
- •Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine
- •Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders
- •Previous or ongoing significant chronic renal dysfunction
- •Previous or ongoing malignancy other than pancreatic cancer < five years prior to enrolment, except basal cell carcinoma treated locally
- •Cardiovascular disease, New York Heart Association (NYHA) classification III or IV16
- •Severe pulmonary obstructive or restrictive disease
- •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)
- •PT/PTT > 1.5 x ULN
- •Serum creatinine > 130 μmol/l) or clearance < 60 ml/min
- •AST and/or ALT > 3 x ULN with the exception of patients with liver metastasis (> 5 x ULN)
- •Alkaline phosphatase > 3 x ULN
- •Total bilirubin > 3 x ULN
- •Immunotherapy within six weeks prior to enrolment.
- •Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrolment
- •Any radiotherapy for pancreatic adenocarcinoma before enrolment except for treatment of bone metastases if target lesions are not included in the irradiated field
- •Major surgery within four weeks prior to enrolment
- •Pregnant or nursing woman
- •Participations in other interventional clinical study within four weeks of enrolment
研究组 & 干预措施
AXP107-11
干预措施: AXP107-11 (Drug)
结局指标
主要结局
Determine the safety profile and the maximum tolerated dose (MTD) of AXP107-11 alone and when given in combination with gemcitabine standard therapy.
时间窗: up to 6 months
Safety (AEs, dose limiting toxicity, laboratory tests, vital signs, weight and ECG). MTD is defined at day 8.
To assess the effect of a combination therapy of AXP107-11 and gemcitabine on objective response rate defined as the percentage of patients who showed complete response (CR) or partial response (PR).
时间窗: up to 6 months
The tumour response evaluation will be performed according to RECIST (www.recist.org)
次要结局
- To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11.(Day -13, 1, 8 and 15)
- To assess the safety and tolerability of a combination therapy of AXP107-11 and gemcitabine.(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival (OS).(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival rate at six months after start of combination therapy.(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on time to progression (TTP).(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on palliation, defined as the percentage of patients who showed CR, PR or stable disease (SD).(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on clinical benefit response, a composite of measurements of pain (pain intensity and analgesics consumption), Karnofsky performance status and weight.(up to 6 months)
- To assess the effect of combination therapy of AXP107-11 and gemcitabine on the tumor mass using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET).(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on symptom distress score as measured by the Edmonton Symptom Assessment System (ESAS).(up to 6 months)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on quality of life as assessed by the EORTC QLQ-C30 questionnaire and the PAN26 module.(up to 6 months)