Phase-2 Study Evaluating Overall Response Rate (Efficacy) and Autonomy Daily Living Preservation (Tolerance) of "FOLFIRINOX " Pharmacogenetic Dose Adjusted, in Elderly Patients (70 yo. or Older) With a Metastatic Pancreatic Adenocarcinoma.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 11
- 主要终点
- 1st step analysis : Safety and efficacy after 34 patients included
研究概览
简要总结
Metastatic pancreatic carcinomas represent the 5th cause of cancer death in France (#8000 per year). The median age at diagnosis is 69 and 74 in male and female respectively. When the 5-Fluorouracile has been used as a single agent with a limited efficacy during more than 20 years, the onset of gemcitabine in 1995 has led to a moderate increase of median survival (from 4.41 to 5.65 months) and overall survival at 1 year (2 versus 18%). Recently, in a phase II followed by a phase-III study, a French collaborative group has demonstrated the benefit of "FOLFIRINOX " regimen versus gemcitabine alone, in terms of median survival (11.1 versus 6.8 months), progression-free survival (6.4 versus 3.3 months) and response rate (31.6 versus 9.4%).
Although more hematologic (neutropenia) and GI toxicities were observed, FOLFIRINOX was acceptable as a new standard regimen for the majority of patients under the age of 70 with a good Performans Status. To reduce the toxicity of FOLFIRINOX in elderly patients (> 70 yo), pharmacogenetic monitoring of 5-FU and Irinotecan key metabolism enzymes (DPD and UGTA1) may be easily performed. The methodology of the study is to use the Bryant & Day statistical method, allowing to consider simultaneously as principal objective, the response rate (efficacy) and the tolerance (preservation of autonomy daily living, Katz index): this design is particularly fitting in a study for elderly patients who represent half of the pancreatic carcinoma population.
详细描述
METHODOLOGY :
Phase II study, opened, multicentric
MAIN OBJECTIVE :
The main objective is the simultaneous evaluation of the objective rate of answer and toxicity of her(it) of the protocol FOLFIRINOX administered to doses adapted at patients of 70 and more years old.
SECONDARY OBJECTIVE :
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven ductal pancreatic carcinoma
- •Metastatic disease
- •First-line treatment : No previous chemotherapy in metastatic stage but adjuvant treatment before relapse (secondary metastatic) is permitted, provide it has been administered more than 6 months before)
- •Age of 70 yo or above
- •Normal DPD enzyme level or partial defect (excluding total defect)
- •Adequate bone marrow reserve: as indicated by : neutrophils >1500/mm3, platelets >100,000/ mm3, Hb >10.0g/dL.
- •Adequate Renal function as indicated by: MDRD creatinine clearance > 50ml/min.
- •Adequate hepatic function as indicated by: serum bilirubin < 1.5 times the upper limit of normal, AST and ALT < 2.5 times the upper limit of normal, or < 5 times the upper limit of normal if liver metastases are present.
- •Written informed consent must be obtained prior to protocol-specific procedures are being performed
- •Patient is affiliated to a social security category
排除标准
- •Other than ductal pancreatic carcinoma: namely endocrin tumors, acinar cells carcinoma, cystadenocarcinoma or adenocarcinoma of the ampulla of vater
- •Non-metastatic but locally advanced pancreatic adenocarcinoma
- •Complete DPD deficiency
- •History of Cardiac failure or symptomatic coronary artery disease
- •Autonomy Daily Living score by Katz <4
- •Prior treatment with FOLFIRINOX (adjuvant)
- •Major comorbidity likely to be an obstacle to treatment
- •Active or uncontrolled infection such as HIV or chronic B or C hepatitis
- •Uncontrolled diabetes mellitus
- •Prior peripheral neuropathy, grade > 2
- •Inflammatory bowel disease localized on the colon or rectum; bowel obstruction or severe uncontrolled diarrhea
- •Previous or concomitant malignancies other than effectively treated carcinoma in situ of the cervix or non-melanoma skin cancer
- •Hereditary fructose intolerance
- •Persons deprived of liberty or under guardianship
- •Any social, geographical or psychological condition which would compromise the ability to fully comply with the trial procedures and treatments
研究组 & 干预措施
FOLFIRINOX
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
干预措施: Folinic acid (Drug)
FOLFIRINOX
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
干预措施: Oxaliplatine (Drug)
FOLFIRINOX
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
干预措施: 5-FU (Drug)
FOLFIRINOX
FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU
干预措施: Irinotecan (Drug)
结局指标
主要结局
1st step analysis : Safety and efficacy after 34 patients included
时间窗: 12 weeks after the 34th patient included
Evaluation of Efficacy: Progression-free-Survival (PFS) and Overall Survival (OS) will be evaluated. Evaluation of Toxicity: Will be analyzed, according to the NCI-CTCAE version 4.0: * The incidence of hematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia) * The incidence of GI toxicities, in particular diarrhea and oral mucositis * The incidence of peripheral neuropathies For statistical analysis : either \>= 17 patients show a decrease of their ADL (of 1.5 ADL or more) : the treatment is considered as being too toxic, either \<= 3 patients presented a tumoral response: the treatment is considered as not being effective enough, =\> The study will then be arrested in this 1st stage.
Composite Safety and Early Efficacy Assessment in the First 34 Patients
时间窗: From treatment initiation through Week 12
This outcome is a composite assessment combining safety and early efficacy signals in the first 34 enrolled patients. Safety is measured by the occurrence of grade ≥3 toxicities (NCI-CTCAE v4.0). Early efficacy is assessed by the presence or absence of tumor response according to predefined stopping rules. Both components contribute jointly to the decision-making criteria for continuation of the study. This description corresponds specifically to the data reported in the Results section.
次要结局
- 2nd step analysis : Safety and efficacy after 72patients included(12 weeks after the 72th patient included)