A Phase III, Open Label, Multicentre Randomised Clinical Study Comparing Acelarin (NUC-1031) With Gemcitabine in Patients With Metastatic Pancreatic Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 328
- 试验地点
- 1
- 主要终点
- Number of participants that have survived throughout treatment and also into follow-up, as measured by the primary cause of death and date of death CRFs.
研究概览
简要总结
The primary purpose of this study is to assess whether Acelarin (NUC-1031) is superior to gemcitabine in terms of overall survival for treatment of patients with metastatic pancreatic carcinoma. In addition disease progression, quality of life and comparative safety will be evaluated. Secondary objectives are to compare between the two treatment groups the following:
- Progression Free Survival (PFS)
- Radiological Response and disease control rate
- Toxicity and safety
- Quality of Life
Additional, exploratory objectives are to discover and validate possible biomarkers to predict additional benefit of Acelarin (NUC-1031) over gemcitabine alone.
详细描述
Pancreatic cancer remains the most lethal of solid tumours with little progress being made to improve patient outcomes over the past 30 years of research. The incidence in the UK is approximately 9,000 new cases per year and, with a 5 year survival remaining at just 3%, mortality approximates incidence. These dismal outcomes reflect:
- Advanced stage at presentation such that only a minority of patients are suitable for surgery with curative intent;
- High rates of recurrence even in those undergoing radical surgery;
- Limited efficacy of systemic therapies.
Until recently, the mainstay of systemic therapy for advanced pancreatic cancer was gemcitabine, based on the pivotal study in 1997 by Burris et al., reporting a survival and clinical benefit when compared with 5-FU. However, this benefit is modest with median and 1-year survival of approximately 6 months and 20% respectively for patients with metastatic disease. Combination chemotherapy has shown more promising results but at the expense of significant toxicity limiting this to younger patients with good performance status.
Although these chemotherapy combinations confer a survival advantage over gemcitabine, their use is restricted to a cohort of patients able, and willing, to tolerate additional toxicity. Pancreatic cancer is commonly associated with:
(i) increasing age; (ii) co-morbidities (for example, diabetes mellitus which, if associated with peripheral neuropathy, may limit the safe administration of neurotoxic drugs such as oxaliplatin and nab-paclitaxel); (iii) symptoms that negatively impact on performance status; (iv) biliary obstruction requiring stenting, with associated risks of sepsis and impaired drug metabolism.
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.
- •Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.
- •Metastatic disease precluding curative surgical resection or definitive locally directed therapies such as chemo radiation. Patients who have relapsed following previously resected pancreatic cancer can be included.
- •Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment.
- •Unidimensionally measurable disease.
- •ECOG performance status 0, 1 or 2 where combination chemotherapy is not deemed appropriate or is declined by the patient.
- •Platelets ≥100 x 109/l; WBC ≥ 3 x 109/l; neutrophils ≥ 1.5 x 109/l at entry.
- •Documented life expectancy > 3 months.
- •Informed written consent.
排除标准
- •Laboratory results:
- •Serum bilirubin ≥ 1.5x the upper limit of reference range (ULRR).
- •Haemoglobin < 10G/dl.
- •Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula).
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULN or > 5x ULN if judged by the investigator to be related to liver metastases.
- •Medical or psychiatric conditions compromising informed consent.
- •Intracerebral metastases or meningeal carcinomatosis.
- •Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol.
- •Pregnancy or breast feeding.
- •Previous chemotherapy for locally advanced and metastatic disease. Adjuvant chemotherapy for resected pancreatic cancer will be permitted provided that chemotherapy was completed > 12 months previously.
- •Radiotherapy within the last 4 weeks prior to start of study treatment.
- •Concurrent malignancies or invasive cancers diagnosed within past 5 years except for adequately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix or resected pancreatic cancer.
- •Hypersensitivity to gemcitabine or any of the excipients of gemcitabine or Acelarin (NUC-1031).
- •All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be from the list below, the other must be a condom* or abstaining from sexual intercourse, until six months after treatment has ended:
- •Combined (oestrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal.
- •Progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable.
- •Intra-uterine device (IUD)
- •Intra-uterine hormone-releasing system (IUS)
- •Bilateral tubal occlusion
- •Vasectomised partner *Male or female condom with or without spermicide is not an acceptable method of contraception alone.
研究组 & 干预措施
Acelarin (NUC-1031)
825 mg/m2 administered intravenously over 15 to 30 minutes on days 1, 8 and 15 of a 28 day cycle.
Patients will be seen on a weekly basis during the time they are on active treatment and will be treated until disease progression.
干预措施: Acelarin (Drug)
Gemcitabine
Gemcitabine: 1000mg/m2 administered intravenously as a 30 minute infusion on days 1, 8 and 15 of a 28 day cycle.
Patients will be seen on a weekly basis during the time they are on active treatment and will be treated until disease progression.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Number of participants that have survived throughout treatment and also into follow-up, as measured by the primary cause of death and date of death CRFs.
时间窗: 4 years
次要结局
- Number of participants that survive progression-free and for how long, as assessed by 12-weekly CT scan assessments per RECIST v1.1 and end of study CRF to capture the reasons for coming off study.(4 years)
- Number of participants that show an objective response, as demonstrated by 12-weekly CT scan assessments per RECIST v1.1.(4 years)
- Number of participants deemed to have disease control, as demonstrated by 12-weekly CT scan assessments per RECIST v1.1.(4 years)
- Number of patients with treatment-related adverse events as assessed by CTCAE v4.03. Toxicity is assessed by CTCAE v4.03 alongside Quality of Life Questionnaires, QLQ-C30 and QLQ-PAN26.(4 years)