Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine Chemotherapy for Pancreatic Cancer Peritoneal Metastases - A Single-arm, Open-label, Phase II Trial: Nab-PIPAC Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Disease Control Rate (DCR)
研究概览
简要总结
Combined chemotherapy consisting of endovenous Nabpaclitaxel-Gemcitabine and Nabpaclitaxel-PIPAC may be a promising treatment for patients affected by pancreatic cancer PM who are in need of curative options.
The purpose of this study is to evaluate the antitumoral activity of combined Nabpaclitaxel-PIPAC and systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases.
Secondary objectives include the evaluation of the feasibility, the safety, further assessment of the antitumoral activity, the overall and progression free survival, the QoL, the pharmacokinetics of Nabpaclitaxel PIPAC.
Furthermore, the study aims to evaluate the patients' nutritional status and the molecular evolution of PM along treatment with a time-course translational research.
详细描述
Pancreatic carcinoma (PC) is an aggressive neoplasm carrying a high metastatic potential with a 5-year survival rate of 7%. The vast majority of cases already developed locally advanced disease, and distant metastases are present at the time of diagnosis. Furthermore, the recurrence rate is nearly 80% within the first two years after surgery, and about half of these patients show peritoneal relapse. Palliative systemic chemotherapy represents the standard treatment option in case of peritoneal metastases (PM) from PC but roughly reaches a median overall survival of 6-11 months with more than 5% of serious adverse events.
Based on the available data, Nabpaclitaxel is indicated in combination with Gemcitabine for the first-line systemic treatment of patients with metastatic adenocarcinoma of the pancreas.
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a novel intraperitoneal drug-delivery system of low-dose chemotherapy as a pressurized aerosol. Until now, the combination cisplatin/doxorubicin or oxaliplatin has been administered by PIPAC. Recently, a phase I study (NCT03304210) was conducted to explore the use of intraperitoneal Nabpaclitaxel administered by PIPAC, confirming its safety and preliminary efficacy. The recommended dose to safely start a phase-II study was 112.5 mg/m2.
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
- •Age ≥ 18 years;
- •Willing and able to provide written and informed consent;
- •Histological or cytological proof of pancreatic cancer;
- •Metastatic disease with peritoneal carcinomatosis determined by the treating physician, based on abdominal CT or MR and/or diagnostic laparotomy or laparoscopy;
- •Evaluable disease defined by RECIST 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- •Life expectancy of at least 3 months;
- •No contraindication for laparoscopy;
- •No contraindication for drugs used in the study;
- •Adequate bone marrow function: Absolute neutrophil count ≥ 1500 cell./mm3; Platelets ≥ 100000 cell./mm3;
- •Hemoglobin ≥ 9 g/dl
- •Adequate renal function (serum creatinine up to 1.5 times the maximal limit of the local laboratory) or else based upon clinical evaluation;
排除标准
- •Advanced metastatic systemic disease with clinical deterioration;
- •Patients with extraabdominal tumor spread;
- •Patients with a germline or somatic pathogenic variant involving an (Homologous Recombination Repair) HRR-related gene;
- •Symptoms of gastrointestinal occlusion and total parenteral nutritional support;
- •Patients defined as "refractory" to previous systemic treatment with Nab-paclitaxel and Gemcitabine administered for locally advanced pancreatic cancer (patients treated with Nabpaclitaxel-Gemcitabine for a locally advanced disease may be included if PM developed after at least 6 months from the end of previous chemotherapy);
- •History of severe and unexpected reactions to Nabpaclitaxel or Gemcitabine derivates
- •Known hypersensitivity reaction to drugs chemically related to Nabpaclitaxel, Gemcitabine and their excipients;
- •Severe cardiac disease (recent myocardial ischemia, severe cardiac arrhythmias, severe cardiac failure);
- •Clinical disease progression after first 2 months of systemic Nabpaclitaxel Gemcitabine chemotherapy;
- •Any concurrent severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk of associated with study participation or investigational product administration or may interfere with compliance with study procedures or the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into the study;
研究组 & 干预措施
Interventional
Eligible patients affected by pancreatic cancer PM will be enrolled according to in-/exclusion criteria.
Each patient will be scheduled for three treatment combined courses for a total of six cycles of endovenous Nabpaclitaxel-Gemcitabine chemotherapy and three of Nabpaclitaxel-PIPAC.
干预措施: Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine (Drug)
结局指标
主要结局
Disease Control Rate (DCR)
时间窗: Three and a half years
The Disease Control Rate (DCR) defined as the combined incidence of complete response (CR), partial response (PR) and stable disease (SD) according to the RECIST v. 1.1 criteria during study treatments and the EOT visit.
次要结局
- Antitumoral activity assessed by ascites volume(Three and a half years)
- The compliance to treatment(Three and a half years)
- Toxicity assessed by CTCAE(Three and a half years)
- Antitumoral activity assessed by PRGS(Three and a half years)
- Antitumoral activity assessed by PCI(Three and a half years)
- The Overall Survival (OS)(From treatment start to death, assessed up to 12 months)
- Postoperative complication assessed by Clavien-Dindo(Three and a half years)
- Antitumoral activity assessed by tumor markers(Three and a half years)
- The Progression Free Survival (PFS)(From treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months)