Phase I Trial of Intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM) for Treatment of Peritoneal Carcinomatosis
概览
- 阶段
- 1 期
- 干预措施
- Paclitaxel-loaded tumor penetrating microparticles
- 疾病 / 适应症
- Peritoneal Carcinomatosis
- 发起方
- Carlos Chan
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Assess safety of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
- 状态
- 终止
- 最后更新
- 2个月前
概览
简要总结
A first-in-human, unblinded, phase I trial of Paclitaxel-loaded tumor penetrating microparticles (TPM) in peritoneal carcinomatosis patients who are not eligible for standard-of-care therapeutic interventions.
详细描述
This is a first in human study of Paclitaxel-loaded TPM, suspended in 0.5 L of 0.1% polysorbate 80 in normal saline instilled into the peritoneal cavity. An enrolled patient will (a) undergo laparoscopy during which time the hydrostatic pressures at different locations within the peritoneal cavity are measured, pretreatment tumors are biopsied and peritoneal catheter is placed, (b) receive intraperitoneal TPM during index hospital stay, and (c) followed-up to evaluate treatment-related toxicity and response. The pharmacokinetics of TPM and paclitaxel in peritoneal fluid and systemic blood samples will be measured. Second dose of TPM is given in clinic if no disease progression or significant AEs. This is a dose escalation study. Dose escalation will proceed using an accelerated titration design (ATD) with intra-patient dose escalation. In the event either: * 1 patient exhibits DLT during the first course of treatment or * 2 patients exhibit grade 2 study drug-related (attribution of probable or definite) toxicity during the first course of treatment. The design switches to a standard 3+3 design at the dose that triggered the switch-two additional patients are accrued at this dose level. Decisions on when and how to escalate if the design switches to a 3+3 are described in the protocol section 6.3
研究者
Carlos Chan
Assistant Professor
University of Iowa
入排标准
入选标准
- •Ability to understand and the willingness to sign a written informed consent document
- •Have pathology proven peritoneal carcinomatosis (PC) due to colorectal, ovarian, gastric, pancreatic, appendiceal cancer or mesothelioma, or suspected peritoneal metastasis based on radiological findings. (Patient to come off study if no pathology evidence of peritoneal metastasis at the time of surgery)
- •No other standard treatment options are available
- •Measurable intraperitoneal disease by RECIST v1.1 criteria , or by radiological PCI scoring when RECIST is not feasible, on imaging studies
- •18 to 75 years of age
- •Have an ECOG performance of 0 to 2
- •Have adequate organ and bone marrow functions as indicated by:
- •Leukocytes ≥ 3000/mcL
- •Absolute neutrophil count ≥ 1500/mcL
- •Platelets ≥ 100000/mcL
排除标准
- •Presence of mucinous ascites
- •Evidence of extra-peritoneal metastases
- •Current or expected use of other investigational agents
- •Received systemic chemotherapy or radiotherapy within 3 weeks prior to study enrollment or not recovering from adverse events (e.g., recovery to ≤ Grade 1)
- •Abdominal cavity deemed not accessible by treating surgeon due to prior abdominal surgery
- •History of allergic reactions to paclitaxel, PLG co-polymer, mannitol, or polysorbate 80
- •Uncontrolled intercurrent illness
- •Currently active second malignancy other than non-melanoma skin cancer
- •Pregnancy, nursing, or plans to become pregnant for the duration of study participation including 10 months beyond the last dose of TPM
- •Grade 2 or higher peripheral neuropathy
研究组 & 干预措施
Intraperitoneal paclitaxel-loaded tumor penetrating microparticles (TPM)
Paclitaxel-loaded tumor penetrating microparticles (TPM), dose escalation starting at 50 mg/m\^2 instilled in the peritoneal cavity at study start and again 6-8 weeks after the first TPM treatment.
干预措施: Paclitaxel-loaded tumor penetrating microparticles
结局指标
主要结局
Assess safety of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
时间窗: 12 Weeks
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0 grades), and relation to study treatment using the safety population.
Determine the maximum tolerated dose (MTD) of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)
时间窗: 4 Weeks
Dose escalation will proceed using an accelerated titration design (ATD). Subjects will be observed for 4 weeks after the first course of TPM treatment for any potential dose limiting toxicities (DLT). The MTD is defined as the highest dose level for which at most 1 out of 6 patients experience a DLT.
次要结局
- Assess potential therapeutic efficacy of intraperitoneal Paclitaxel-loaded Tumor Penetrating Microparticles (TPM)(12 Weeks)
- Measure maximum drug concentration of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid(8 Weeks)
- Assess whether Paclitaxel-loaded Tumor Penetrating Microparticles (TPM) induce immune response in the peritoneal cavity(8 Weeks)
- Measure area-under-drug concentration-time curve of Paclitaxel and tumor penetrating microparticles (TPM) in blood and peritoneal fluid(8 Weeks)
- Assess whether intra-abdominal pressure is location-dependent(Day 1 on study)