Metronomic Neoadjuvant Capecitabine and Cyclophosphamide in Huge (PCI>28) Pseudomyxoma Peritonei Patients Candidates to Cytoreductive Surgery (CRS) and Hypertermic Intraperitoneal Chemotherapy (HIPEC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- The proportion of patients with complete cytoreduction after neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and efficacy of neoadjuvant capecitabine and cyclophosphamide treatment in patients affected by huge Pseudomyxoma peritonei (PMP) (peritoneal cancer index >28). Treatment consists of metronomic (low-dose medication for a prolonged time) of capecitabine plus cyclophosphamide for 6 months followed by standard of care cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The main question the trial aims to answer is which is the proportion of patients with complete cytoreduction at CRS/HIPEC after neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.
详细描述
Mucinous neoplasms are the most common appendiceal tumors, and the most common cause of Pseudomyxoma peritonei (PMP). The term PMP defines a clinical syndrome characterized by progressive accumulation of mucinous material within the abdominal-pelvic cavity, ultimately leading to patient death due to local-regional progression of the disease. The upfront cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as standard treatment for PMP.
However, not every PMP patient benefit from upfront CRS and HIPEC. A proportion of patients could be inoperable due to a lack of clinical conditions for clinical deterioration or comorbidites contra-indicating surgery, or an unresectable disease at the diagnosis. Up to 32% of cases could be present the so-called huge PMP (peritoneal cancer index >28), where the proportion of patients with complete cytoreduction is low of their entire cohort of PMP patients. Moreover, CRS in huge PMPs generally requires very extensive surgical maneuvers such as total gastric or total colon resection. Hence, the patients suffer from a significant impact on postoperative quality of life due to nutritional issues.
Preoperative systemic chemotherapy might be an option for such advanced cases, as it can possibly reduce the tumor burden, allowing less extensive surgery with less visceral resections. Systemic treatment regimens are associated with relevant toxicity and highcosts. Metronomic schedules might be preferred because of their favorable safety profileand antiangiogenic and immunomodulatory properties.
In unresectable or progressive PMP, a single-center prospective uncontrolled trial showed the safety and promising activity results of a continuous metronomic regimen with capecitabine with cyclophosphamide. At a median follow-up of 22.4 months, median progression-free survival was 9.5 months, and the 1-year overall survival rate was 73.7%. Overall, the disease control rate was 87%, and 6 (27%) patients achieved disease control ≥12 months.
On this basis, a phase II, mono-institutional, single arm trial was designed, evaluating neoadjuvant metronomic capecitabine and cyclophosphamide in patients affected by huge Pseudomyxoma peritonei who are potentially candidates to cytoreductive surgery and HIPEC. The goal of the present study is to evaluate the surgical and oncological outcomes of neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.
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 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical/Histological diagnosis of pseudomyxoma peritonei (PMP);
- •Peritoneal Cancer Index (PCI >28) assessed by chest and abdominal CT scan at the staging phase;
- •Age >= 18 years and <76 years;
- •Performance Status (ECOG <2);
- •Adequate organ function including the following:
- •Adequate bone marrow reserve: WBC count >3.0x109/L, absolute neutrophyl count >1.5x109/L, platelet count >100x109/L, and hemoglobin >10 g/dL;
- •Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase < 2.5 x UL;
- •Renal: Creatinine clearance >50 mL/min or serum creatinine <1.5 x UNL;
- •Patients compliance and geographic proximity that allows for adequate follow-up;
- •Patients must sign an informed consent document (ICD);
- •Male and female patients with reproductive potential must use an approved contraceptive method;
排除标准
- •Peritoneal Cancer Index (PCI ≤28) assessed by chest and abdominal CT scan at the staging phase;
- •DPD deficiency;
- •Previous systemic chemotherapy and/or biological therapy;
- •Administration of other experimental drugs during the study Pregnancy and breast-feeding;
- •Serious or uncontrolled medical pathologies or active infections that would jeopardize the possibility of receiving the investigated treatment;
- •Disorders that could influence the absorption of capecitabine (e.g. malabsorption), intestinal occlusion, Crohn's disease or ulcerative colitis;
- •Psychiatric disorders, neurologic disease or other conditions that would make it impossible to comply with the protocol procedures;
- •Positive anamnesis with regard to other neoplastic diseases except for the ones that have been cured for more than 5 years.
结局指标
主要结局
The proportion of patients with complete cytoreduction after neoadjuvant metronomic approach with oral capecitabine and cyclophosphamide in patients affected by huge PMP.
时间窗: 6-8 months from the start of treatment
Use of Completeness of Cytoreduction score to evaluate the radicality of Cytoreductive Surgery. Patients with a residual disease \<2.5 mm will be considered completely cytoreduced, otherwise incompletely cytoreduced. "Completeness of Cytoreduction Score" ranging from the best cc-0: no peritoneal nodule was seen, afterwards cc-1,tumor nodules persisting after cytoreduction are less than 2.5 mm in diameter, then cc-2, tumor nodules persisting after cytoreduction are between 2.5 mm and 2.5 cm in diameter to the worst cc-3, tumor nodules persisting after cytoreduction are greater than 2.5 cm
次要结局
- Radiological objective tumor response rate.(Performed at baseline and 16 weeks from the start of treatment.)
- Conversion rate(6-8 months from the start of treatment)
- Downsizing of the tumor measured by surgical Peritoneal Cancer index (PCI).(Performed after 16 weeks.)
- Safety and tolerability of neoadjuvant metronomic chemotherapy.(6-8 months.)
- Major complications (NCI-CTCAE v5) associated with CRS and HIPEC(30 days after surgery.)
- Quality of life EQ-5D-5L(Before/after neoadjuvant metronomic chemotherapy, and 30 days after the surgery.)
- Progression-free survival(After 24 months.)
- Overall Survival.(After 48 months.)
- Quality of life EORTC-QLQ-C30(Within 30 days after the date of surgery.)