Phase I / II Dose Escalation of Oxaliplatin Via a Laparoscopic Approach of Aerosol Pressurized Intraperitoneal Chemotherapy for Nonresectable Peritoneal Metastases of Digestive Cancers (Stomach, Hail and Colorectal)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 34
- 试验地点
- 3
- 主要终点
- Maximal Tolerated Dose
研究概览
简要总结
Current curative treatment of digestive peritoneal carcinomatosis consists of complete cytoreduction surgery associated with intraperitoneal chemotherapy. This treatment has important limits: a high morbimortality and the impossibility of repeating the sessions. The majority of patients are therefore treated with systemic chemotherapy, which despite its progress, remains palliative.
Pressurized Intraperitoneal aerosol chemotherapy (PIPAC) has many advantages: under laparoscopy, low morbidity, good intratumoral penetration of cytotoxics, possibility of repeating the sessions and low financial cost.
Therefore, the investigator propose a phase 1 study, in colorectal and stomach cancer, with oxaliplatin doses escalation in Pressurized Intraperitoneal aerosol chemotherapy. It would allow a better tumor response, with potentially few risks and thus improve survival in patients with digestive peritoneal carcinoses, increasing access to cytoreductive surgery.
详细描述
The objective of this study is to determine the maximum tolerated dose (mtd) of oxaliplatin to be used during PIPAC.
Study design is a phase I/II, multicentre, non-comparative, non-randomised dose escalation clinical trial.
The phase I study will consist of a 3 by 3 dose escalation according to modified fibonacci dose escalation, starting at the current PIPAC dose (i.e. 90mg/m2), up to a maximum dose of 300mg/m2, corresponding to the current Intraperitoneal chemohyperthermia.
Each patient may receive up to 5 PIPAC sessions ; DLT period will be from the first day (D1) of the first PIPAC session until the end of the second PIPAC session, including the interval chemotherapy (i.e. D-1 of the 3rd CIPPA session), i.e. 4 to 6 weeks later ; Phase II study is an extension cohort at the recommended dose determined in the Phase I study. It will be a multi-centre, single-arm study and will analyse overall patient survival and secondary resectability rates with complete cytoreductive surgery and intraperitoneal chemohyperthermia. It will be conducted in approximately 20 patients treated at the recommended dose and followed for 2 years.
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
- •Patient age ≥ 18 years
- •Histological or cytological diagnosis or suspicion of peritoneal carcinosis of colorectal, gastric or bowel origin
- •Having previously received at least 3 months of systemic chemotherapy for metastatic disease (type of chemotherapy left to the discretion of each investigator). Patients who received bevacizumab (Avastin®) can be included if and only if the time between the last treatment administered and the first PIPAC received is at least 4 weeks
- •ECOG performance index < or = 2
- •Life expectancy> 3 months
- •Peripheral neuropathy grade ≤ 1
- •Hematological function: Hemoglobin ≥ 9 g / dL, leukocytes ≥ 4000 / mm3, PNN ≥ 1500 / mm3, platelets ≥ 100 000 / mm3
- •Creatinine clearance> 50 mL / min (cockcroft and Gault formula)
- •Hepatic function: Total bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 3 x ULN, Alkaline phosphatases ≤ 3 x ULN 10 . Patients with no known or partial deficiency of Dihydropyrimidine dehydrogenase (i.e. DPD)
- •Effective contraception for women of childbearing age
- •Informing the patient and obtaining free, informed and written consent signed by the patient and his / her investigator.
- •Affiliated subject or beneficiary of the social security scheme.
排除标准
- •Patients who received bevacizumab (Avastin®) less than 4 weeks ago can not be included
- •Extra-peritoneal metastases, except for less than 3 pulmonary nodules (each size <5mm)
- •Known hypersensitivity to Oxaliplatin
- •Known complete dihydropyrimidine dehydrogenase (i.e. DPD) deficiency
- •Peripheral neuropathy Grade >1 due to or not with Oxaliplatin previously used
- •Active or other serious underlying disease that may prevent the patient from receiving treatment
- •Intracranial or intraocular hypertension (ongoing at the time of inclusion)
- •Severe or Severe Heart Failure (ongoing at the time of inclusion)
- •Complete intestinal obstruction (ongoing at the time of inclusion)
- •Other concurrent cancer or history of cancer other than in situ cancer of treated cervix or basal cell carcinoma or squamous cell carcinoma
- •Pregnant or nursing women
- •Persons deprived of their liberty or under guardianship or unable to give their consent
- •Inability to submit to medical follow-up of the trial for geographical, social or psychological reasons
- •Long-term corticosteroids (duration> 3 months), except for weaning for at least 3 months
研究组 & 干预措施
Oxaliplatin
The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).
干预措施: 5-Fluorouracil (Drug)
Oxaliplatin
The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).
干预措施: L-Folinic acid (Drug)
Oxaliplatin
The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Maximal Tolerated Dose
时间窗: 8 to 12 weeks
Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)
Recommanded dose for the extension phase
时间窗: 8 to 12 weeks
Dose level below the maximum tolerated dose
次要结局
- Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level(24 months after the last PIPAC received)
- Overall survival(24 months after the last PIPAC received)
- Progression-Free Survival(12 months after the last PIPAC received)