Phase II Study of NAB-PACLITAXEL Plus FOLFOX as Perioperative Chemotherapy in Patients With Operable Oesogastric Adenocarcinoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 55
- 试验地点
- 7
- 主要终点
- Complete pathological response rate
研究概览
简要总结
This is a non-randomized pauci-centre, open-label phase II study. The treatment will consist in a chemotherapy by FOLFOX and nab-paclitaxel following modalities determined in the Brown University Phase I study.
In neoadjuvant setting : 3 months of treatment
Main criteria of Withdraw of the treatment: in case of tumor progression, non acceptable toxicity, or patient decision.
Post-operative treatment (for 6 additional cycles) is recommended, but will depend on the result of the neo-adjuvant treatment and the ability of patients to receive adjuvant chemotherapy based on tolerance of neo-adjuvant treatment and general post-operative condition (i.e. adjuvant treatment if no progression during neo-adjuvant chemotherapy, less than 80% of residual viable tumor compared to initial tumor volume, acceptable tolerance and post-operative PS 0 - 2). Adjuvant treatment must be initiated within 8 weeks post-operatively.
详细描述
This is a non-randomized pauci-centre, open-label phase II study. The treatment will consist in a chemotherapy by FOLFOX and nab-paclitaxel following modalities determined in the Brown University Phase I study.
In neoadjuvant setting : 3 months of treatment
Main criteria of Withdraw of the treatment: in case of tumor progression, non acceptable toxicity, or patient decision.
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
- •Signed and dated informed consent, and willing and able to comply with protocol requirements,
- •Histologically or cytologically proven adenocarcinoma of the low oesophagus or of the stomach, (from 1/3 inferior of the oesophagus to pylorus)
- •HER2 negative tumors
- •Localized and operable disease confirmed (stage I-III),
- •No prior therapy for localized disease ,
- •Age ≥18 years,
- •Performance status (PS) 0-2,
- •Haematological status: neutrophils (ANC) > 2.0x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,
- •Adequate renal function: serum creatinine level <150µM and creatinine clearance test > 30mL/min,
- •Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (Upper Limit of Normal)
- •Total bilirubin ≤1.5 x ULN,
- •Albumin ≥25g/L
- •Baseline evaluations performed before inclusion: clinical and blood evaluations no more than 2 weeks (14 days) prior to inclusion, tumor assessment (CT-scan, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to inclusion,
- •Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 72 hours days prior to starting nab-paclitaxel neo-adjuvant and adjuvant treatment. Breastfeeding is not allowed. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment,
- •Registration in a national health care system (CMU included for France).
排除标准
- •Metastatic disease (stage IV)
- •Non operable primary tumor
- •Patient using warfarin,
- •Uncontrolled hypercalcemia (corrected serum calcium > 2.55 mmol/l),
- •Pre-existing permanent neuropathy (NCI grade ≥2),
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency,
- •Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
- •Treatment with any other investigational medicinal product within 28 days prior to study entry,
- •Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
- •Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C.
- •Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
- •Patients with known allergy to any excipient of study drugs,
- •Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine and concomitant administration of prophylactic phenytoin
- •Patient with any medical or psychological condition, deemed by the investigator to likely interfere with patient's ability to sign informed consent or cooperate and participate in the study, including tutelage or guardianship.
研究组 & 干预措施
nab-paclitaxel + FOLFOX
nab-paclitaxel + FOLFOX nab-paclitaxel: 150 mg/m2 D1 every 2 weeks Leucovorin: 400 mg/m2 D1 every 2 weeks Oxaliplatin: 85 mg/m2 D1 every 2 weeks 5-FU infusion: 2400mg/m2 48h infusion every 2 weeks 6 pre-operative cycles 6 post-operative cycles (optional)
干预措施: nab-paclitaxel (Drug)
nab-paclitaxel + FOLFOX
nab-paclitaxel + FOLFOX nab-paclitaxel: 150 mg/m2 D1 every 2 weeks Leucovorin: 400 mg/m2 D1 every 2 weeks Oxaliplatin: 85 mg/m2 D1 every 2 weeks 5-FU infusion: 2400mg/m2 48h infusion every 2 weeks 6 pre-operative cycles 6 post-operative cycles (optional)
干预措施: FOLFOX (Drug)
结局指标
主要结局
Complete pathological response rate
时间窗: after three months of neoadjuvant chemotherapy
次要结局
- Disease Free Survival (DFS)(time from the date of inclusion up to the date of disease progression or death whichever occurs last up to 7 years)
- Overall Survival (OS)(time interval form the inclusion to the date of the death from any cause up to 7 years)
- Health related to Quality of Life (QoL)(up to 8 months)
- Assessment of biomarkers when appropriate(1 day of biopsie from diagnosis, and tumor from surgery)
- Assessment of genetic polymorphism involved in tumor-response when appropriate(28 days after last study treatment)
- Safety profile of the combination of nab-paclitaxel + FOLFOX regimen assessed by adverse events(time from randomisation up to end of study up to 7 years)