Phase I Trial of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Patients With Peritoneal Metastasis From Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- To confirm the safety and tolerability of PIPAC with nab-paclitaxel in conjunction with medical oncologist choice standard of care therapy with CTCAE v5.0
研究概览
简要总结
Palliative systemic therapy is the standard treatment option for patients with pancreatic ductal adenocarcinoma (PDAC) and peritoneal metastasis (PM), who have a median overall survival of only 6-11 months and a serious adverse event (SAE) rate of >5%. Patients with peritoneal-only metastasis may demonstrate unique tumor biology with less potential for hematogenous and lymphatic spread, making them potential candidates for a regional approach directed at the peritoneum. PIPAC is a drug- delivery system that combines the pharmacokinetic advantages of low- dose intraperitoneal chemotherapy (high tumor tissue penetration with low systemic absorption/toxicity) with the principles of aerosolization (homogenous intraperitoneal distribution and deeper tissue penetration). PIPAC may offer a complimentary approach to maximize drug delivery to tumor implants, potentially improving quality of life and survival without significant additional morbidity. Several non-randomized studies have evaluated safety, feasibility, and efficacy of PIPAC with various intraperitoneal agents in a variety of tumor types. Very few patients with pancreatic cancer PM have been included in these studies and most have been treated with either PIPAC-oxaliplatin or doxorubicin/cisplatin. A recent phase 1 dose-escalation study included patients with ovarian, gastric, breast, and hepatopancreatobiliary malignancies. One patient with
pancreatic cancer was included in this study. The recommended phase 2 dose was 140 mg/m2, with guidance to decrease the dose to 112.5 mg/m2 in patients with hepatic impairment. Therefore, the dose utilized in this study is 112.5 mg/m2. This recommendation was based on concern for nab-paclitaxel hepatotoxicity, but there was no data presented to support this expert recommendation.
This study sets out to explore the role of PIPAC with nab-paclitaxel in combination with medical oncology choice standard of care therapy in this patient population.
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
- •Ability to understand and sign informed consent form
- •Age ≥18 years
- •Patient must have histologically confirmed pancreatic adenocarcinoma with either histologic confirmation or strong suspicion of peritoneal metastasis on cross sectional imaging
- •ECOG performance status ≤ 2
- •Pre-treatment Laboratory Parameters:
- •Absolute neutrophil count (ANC) > 1500/mm3
- •Platelets > 100,000/mm3
- •Hemoglobin > 9 g/dl
- •Serum total bilirubin < 1.5 x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN, unless patient is known to have chronic liver disease (hepatitis) in which case AST and ALT must be ≤ 5 x ULN.
- •Creatinine clearance (Ccr) > 40 ml/min
- •No contraindications for a laparoscopy.
- •The peritoneal disease does not have to be measurable by RECIST 1.1 but needs to visible on cross sectional imaging or diagnostic laparoscopy.
- •For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- •Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- •Women of childbearing potential (WOCBP) and male patients with WOCBP partner must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 6 months after the PIPAC or last dose of chemotherapy in such a manner that the risk of pregnancy is minimized .-WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
- •Amenorrhea ≥ 12 consecutive months without another cause or For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered of childbearing potential.
- •Inclusion to proceed with PIPAC :
- •Laparoscopy findings must meet all of the below criteria in order to proceed to PIPAC:
- •PIPAC access is feasible
- •There is room for aerosol therapy
- •There is no evidence of impending bowel obstruction
- •< 5 L of ascites
- •Not a candidate for cytoreduction and HIPEC
排除标准
- •Confirmed or suspected extra-peritoneal metastasis
- •Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition.
- •Life expectancy of less than 4 months.
- •Prior intra-abdominal aerosol chemotherapy
- •Previous anaphylactic reaction to the nab-paclitaxel drug used.
- •Intra-abdominal Ascites >5L
- •Patients may not be receiving any other investigational agents.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, severe renal impairment, myelosuppression, or severe hepatic impairment.
- •Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system.
- •New York Heart Association (NYHA) Class 3 or 4; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months.
- •Exclusive total parenteral nutrition.
- •Pregnancy. Patients with psychiatric illness/social situations that would limit compliance with study requirements.
研究组 & 干预措施
Interventional Arm
This study is a prospective single center, non-randomized phase I trial to confirm the safety of PIPAC with nab- paclitaxel in conjunction with standard of care systemic therapy in patients with peritoneal-only metastasis from PDAC. The efficacy signals noted in this trial will inform a potential phase II/III multicenter clinical trial.
Patients may receive up to 3 treatments whilst enrolled on the study, with a potential opportunity to extend outside of the trial for compassionate use.
干预措施: Nab-paclitaxel (Drug)
Interventional Arm
This study is a prospective single center, non-randomized phase I trial to confirm the safety of PIPAC with nab- paclitaxel in conjunction with standard of care systemic therapy in patients with peritoneal-only metastasis from PDAC. The efficacy signals noted in this trial will inform a potential phase II/III multicenter clinical trial.
Patients may receive up to 3 treatments whilst enrolled on the study, with a potential opportunity to extend outside of the trial for compassionate use.
干预措施: PIPAC (Device)
结局指标
主要结局
To confirm the safety and tolerability of PIPAC with nab-paclitaxel in conjunction with medical oncologist choice standard of care therapy with CTCAE v5.0
时间窗: 2 years
DLTs are defined as any of the following events (based on CTCAE v5 and Clavien Dindo) during the first PIPAC cycle and attributable to PIPAC: Any grade 3 or 4 non-hematologic toxicity, excluding: Grade 3 nausea, vomiting, abdominal pain, or diarrhea that is adequately treated to grade 2 or lower within 48 hours. Grade 3 fatigue that returns to grade 2 or less within 7 days. Grade 3 laboratory/metabolic abnormalities that are not considered clinically significant or are easily correctable to grade 2 or lower within 72 hours. Grade 3 infusion-related reaction (first occurrence and in the absence of steroid prophylaxis) that resolves within 6 hours with appropriate clinical management. Grade 3 peripheral neuropathy Surgical complication of Clavien-Dindo grade IIIB or greater
To confirm the safety and tolerability of PIPAC with nab-paclitaxel in conjunction with medical oncologist choice standard of care therapy. Measurement of AEs according to NCI CTCAE version 5.0 during the first cycle, or throughout the 6 weeks following
时间窗: 2 years
Safety: DLTs during the safety evaluation period (6 weeks after initial PIPAC) DLTs are defined as any of the following events (based of CTCAE v5 and Clavien Dindo) during the first PIPAC cycle and attributable to PIPAC: Any Grade 3 laboratory/metabolic abnormality that requires medical intervention, irrespective of the duration of the event Any grade 3 or 4 non-hematologic toxicity excluding: Grade 3 treated nausea, vomiting, abdominal pain, or diarrhea that is adequately treated to grade 2 or lower within 48 hours. Grade 3 fatigue that returns to grade 2 or less within 7 days. Grade 3 laboratory/metabolic abnormalities that are not considered clinically significant or are easily correctable to grade 2 or lower within 72 hours. Grade 3 infusion related reaction (first occurrence and in the absence of steroid prophylaxis) that resolves within 6 hours with appropriate clinical management. Grade 3 peripheral neuropathy Surgical complication of Clavien-Dindo grade IIIB
次要结局
未报告次要终点