IPOXA, Phase I/II Dose Escalation Trial Aiming to Evaluate the Safety of Intraperitoneal (IP) OXAliplatin (OXA) in Association With Systemic FOLFIRI Bevacizumab Chemotherapy in Patients With Peritoneal Carcinosis of Colorectal Origin and Uncertain Resectability.
试验速览
- 阶段
- 1 期
- 入组人数
- 47
- 试验地点
- 6
- 主要终点
- Adverse events (NCI CTCAE v4.0)
研究概览
简要总结
Peritoneal carcinosis (PC) corresponds to a locoregional extension into the peritoneum of rare primary peritoneal cancers, or more frequently distant extension of digestive cancers (colorectal or gastric) or gynecological (ovarian, fallopian tube, or endometrial). PC can be considered as a distinct oncological entity as its genesis, natural history, and response to systematic treatments differ to those of other metastases. The development of PC, observed in 25-35% of colorectal cancers, is generally considered as a unfavorable event in the course of the disease. The prognosis is defined by the possibility of complete resection, possibly after neoadjuvant treatment. The benefit provided by the combination of cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) with respect to systemic chemotherapy in patients with PC of colorectal origin has been demonstrated based on overall survival in several randomized trials, among which one evaluated oxaliplatin. The evaluation of the clinical benefit-risk related to the repeated administration of non-hyperthermic intraperitoneal chemotherapy, as has been validated in ovarian cancer, in patients with PC of colorectal origin is already being investigated by several international teams.
The FOLFOXIRI + bevacizumab every 2 weeks is a modern therapeutic option in patients with this disease. The intraperitoneal rather than intravenous (IV) administration of oxaliplatin, in this combination, could increase the response of peritoneal lesions known to be relatively insensitive to IV chemotherapy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old and ≤ 75 years old
- •ECOG Performance Status (PS) 0-2
- •Peritoneal carcinosis with locoregional extension or metastases of colorectal origin and uncertain resectability
- •PCI > 20 and / or infiltration of the hepatic pedicle and / or necessary digestive tract resections
- •Systemic chemotherapy indication, compatible with the FOLFIRI + bevacizumab combination
- •Satisfactory haematological evaluation: PNN rate greater than 1500 / mm3, platelet count greater than 100 G / l;
- •Satisfactory renal and hepatic function : serum creatinine ≤1.5 times the normal lower values or creatinine clearance ≥50 ml / min, bilirubin ≤1.25 times lower normal values, AST / ALT ≤1.5 times the lower normal values (≤5 times the lower normal values for patients with liver metastases)
- •No unstable conditions: myocardial infarction within 6 months prior to the start of the study, congestive heart failure, unstable angina, active cardiomyopathy, unstable rhythm disorder, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer or any condition that could be aggravated by treatment or limit compliance (investigator assessment);
- •No limitation in the number of previous treatments;
- •Patients may have received conventional cytotoxic chemotherapy , hormonal or immunological targeted biological agents. They should have recovered from previous grade ≤2 toxicities
- •Written informed consent
- •Known RAS status.
排除标准
- •Extraperitoneal metastases for which the site or number preclude potentially curative surgery at any moment during the course of the disease
- •Sign of bowel obstruction or lesions whose topography indicates a risk of intestinal perforation or inflammatory bowel disease
- •ECOG PS 3-4
- •Contraindication to the placement of a intraperitoneal central line
- •Contraindication specifically related to intraperitoneal administration of oxaliplatin
- •known history of hypersensitivity to oxaliplatin or to the excipients
- •peripheral sensory neuropathy grade ≥2
- •Pregnant or lactating women
- •Unable to give consent
- •Patient under legal protection measures
- •Refusal to participate in the study
研究组 & 干预措施
Patients with peritoneal carcinosis
Patients with peritoneal carcinosis of colorectal origin and uncertain resectability with an indication for systemic chemotherapy compatible with the FOLFIRI + bevacizumab combination.
干预措施: intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy (Drug)
结局指标
主要结局
Adverse events (NCI CTCAE v4.0)
时间窗: up to 14 days
The safety of intraperitoneal (IP) administration of oxaliplatin in combination with systemic chemotherapy FOLFIRI + bevacizumab will be evaluated during the first cycle of therapy according to NCI CTCAE version 4.0
Dose Limiting Toxicities, DLT
时间窗: up to 14 days
The safety of intraperitoneal (IP) administration of oxaliplatin in combination with systemic chemotherapy FOLFIRI + bevacizumab will be evaluated during the first cycle of therapy according to Dose Limiting Toxicities
次要结局
- Overall response rate according to RECIST(up to 4 months)
- Peritoneal Cancer Index (PCI)(up to 4 months)
- Adverse events (NCI CTCAE v4.0)(up to 5 months)
- The quality of life (EORTC QLQ-C29)(up to 4 months)
- The quality of life (EORTC QLQ-C30)(up to 4 months)