Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximally Tolerated Dose (MTD) of Abraxane
研究概览
简要总结
The PIPAC nab-pac study is designed to examine the maximal tolerated dose of albumin bound nanoparticle paclitaxel (nab-pac, Abraxane) administered with repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC), in a multicentre, multinational phase I trial.
详细描述
Over 85% of women with ovarian cancer (OC) will develop a peritoneal recurrence after initial therapy. The prognosis of patients with recurrent disease is poor, with a median survival ranging from 12 to 24 months. Most of these patients ultimately develop platinum resistant disease (PROC). Current systemic therapy results in a very modest improvement of progression free and overall survival. The addition of locoregional, intraperitoneal (IP) therapy may improve disease control in recurrent OC. Recently, pressurized intraperitoneal aerosol therapy (PIPAC) was added to the therapeutic arsenal. This novel technique allows repeated laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Abraxane (nab-pac, Celgene) is a novel 130 nm, albumin-bound (nab) nanoparticle formulation of paclitaxel which has noteworthy single-agent activity and a favourable toxicity profile when used systemically in PROC. A recent phase I study showed a significant pharmacokinetic advantage after IP instillation of nab-pac in patients with peritoneal carcinomatosis from ovarian or gastro-intestinal (GI) origin.
In phase I of this study, dose escalation will be combined with pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Phase I study: patients with advanced carcinomatosis from ovarian, breast, gastric, or pancreatic origin. No alternative systemic treatment options are available.
- •Age over 18 years
- •Adequate performance status (Karnofsky index > 60%)
- •Absence of intestinal or urinary obstruction
- •Limited size of the majority of peritoneal tumor implants (< 5 mm)
- •Absent or limited ascites
- •Ability to understand the proposed treatment protocol and provide informed consent
- •Expected life expectancy more than 6 months
- •Laboratory data
- •Serum creatinine ≤ 1.5 mg/dl or a calculated GFR (CKD-EPI) ≥ 60 mL/min/1.73 m²
- •Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert's disease
- •Platelet count > 100.000/µl
- •Hemoglobin > 9g/dl
- •Neutrophil granulocytes > 1.500/ml
- •No major blood coagulation disorders. Parameters within normal range.
- •Absence of alcohol and/or drug abuse
- •No other concurrent malignant disease
- •Written informed consent
排除标准
- •Pregnancy or breast feeding. Women who can become pregnant must ensure effective contraception.
- •Active bacterial, viral or fungal infection
- •Active gastro-duodenal ulcer
- •Parenchymal liver disease (any stage cirrhosis)
- •Uncontrolled diabetes mellitus
- •Psychiatric pathology affecting comprehension and judgement faculty
- •General or local (abdominal) contra-indications for laparoscopic surgery
- •Documented intolerance or allergy to paclitaxel
- •Patients who receive other taxane therapy until three weeks before the first experimental treatment
研究组 & 干预措施
Abraxane 140 mg/m²
PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.
干预措施: PIPAC with Abraxane (Drug)
Abraxane 35 mg/m²
PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
干预措施: PIPAC with Abraxane (Drug)
Abraxane 70 mg/m²
PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.
干预措施: PIPAC with Abraxane (Drug)
Abraxane 90 mg/m²
PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.
干预措施: PIPAC with Abraxane (Drug)
Abraxane 112.5 mg/m²
PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.
干预措施: PIPAC with Abraxane (Drug)
结局指标
主要结局
Maximally Tolerated Dose (MTD) of Abraxane
时间窗: Within 14 weeks of the start of the treatment
The MTD was defined as the highest dose of aerosolized Abraxane, administered 3 times using PIPAC, that does not cause unacceptable side effects. Dose limiting toxicity was recorded in a 14 week-window starting from the first PIPAC and defined a priori as any of the following: 1. any Grade 3 or 4 non-hematologic toxicity excluding fatigue and controllable nausea, vomiting, abdominal pain, and diarrhoea; 2. grade 4 thrombocytopenia; 3. grade 4 neutropenia lasting more than 7 days or associated with fever; 4. failure to perform more than one PIPAC due to toxicity; 5. surgical complication Dindo-Clavien grade IIIB or higher. In order to optimize the balance between safety and efficacy, we used a time-to-event continual reassessment model (TITE-CRM), where an initial design was followed until the first DLT occurred. Conservative a priori estimates of DLT were used to calculate the original dose escalation scheme.
次要结局
- Surgical Morbidity(6 months after third PIPAC)
- Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0(Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC)
- Maximum Plasma Concentration of Abraxane(T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours)
- Area Under The Curve (AUC) of Abraxane(T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours)
- Histological Response Via Peritoneal Regression Grading Scoring (PRGS)(T = 0 minutes, before nebulization)
- Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0(Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC)