A Randomized Phase 2 Trial of Flat Dose vs. Weight-based Dose of Intra-peritoneal (IP) Chemotherapy for Patients Undergoing Cytoreductive Surgery and Heated Intra-peritoneal Chemotherapy (CRS/HIPEC) for Advanced Gastrointestinal Malignancy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Drug Clearance (CL) - Pharmacokinetics
研究概览
简要总结
Peritoneal carcinomatosis from advanced gastro-intestinal malignancy has historically been associated with poor overall survival (≤ 12 months) with few treatment options. Cytoreductive surgery (CRS), which involves removal of all macroscopic tumor nodules, combined with direct administration of heated intra-peritoneal (IP) chemotherapy (HIPEC) to the affected peritoneal surfaces, has been shown to be an effective treatment option that extends overall survival among certain cases of peritoneal carcinomatosis. IP chemotherapy allows delivery of a high dose of cytostatic drug directly onto the peritoneal surfaces at risk for microscopic residual disease while systemic exposure remains limited. Additionally, hyperthermia is known to enhance the cytotoxicity of several agents (including Mitomycin C) and improves the depth of peritoneal penetration.
This trial will be a randomized phase 2 comparison of flat dose versus weight-based dose Mitomycin C. The hypothesis of this study is that HIPEC weight-based dosing may result in similarly effective peritoneal Mitomycin C concentrations with less systemic absorption and potential systemic toxicity, compared with the HIPEC flat dosing approach in patients undergoing CRS/HIPEC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients diagnosed with one of the following: low-grade appendiceal mucinous neoplasm, pseudomyxoma peritonei, appendiceal cancer with peritoneal carcinomatosis, colorectal cancer with peritoneal carcinomatosis
- •ECOG performance status < 3
- •Candidate for grossly complete cytoreductive surgery
- •Life expectancy greater than 3 months
- •Adequate organ and marrow function
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Any extra-abdominal metastases
- •Untreated lung metastases
- •Liver metastases not amenable to resection or ablation
- •Known brain metastases
- •Chemotherapy or radiotherapy within 4 weeks prior to entering the study
- •Presence of residual significant adverse events attributed to prior cancer treatment
- •Currently receiving any other investigational therapeutic agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to Mitomycin C.
- •Pregnant or breast-feeding women
- •Uncontrolled ongoing illness
研究组 & 干预措施
Flat Dose Mitomycin C
Participants in this group will receive flat doses of mitomycin C intra-operatively: 1) 30mg at minute 0 and 2) 10mg at minute 45. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).
干预措施: Mitomycin C, flat dose 40 mg (Drug)
Weight-Based Mitomycin C
Participants in this group will receive weight-based dosing of mitomycin C intra-operatively: 1) 9.5 mg/m2 at minute 0 and 2) 3 mg/m2 at minute 45 for total dose of 12.5 mg/m2. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).
干预措施: Mitomycin C, weight-based dose 12.5 mg/m2 (Drug)
结局指标
主要结局
Drug Clearance (CL) - Pharmacokinetics
时间窗: Approximately 20 hours
Drug clearance will be calculated as the volume of plasma cleared per unit time. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively.
Drug Half-Life (T1/2) - Pharmacokinetics
时间窗: Approximately 20 hours
Drug half-life will be calculated as the time required for the plasma Mitomycin C concentration to be half of its maximum concentration. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively.
Area Under the Curve (AUC) - Pharmacokinetics
时间窗: Approximately 20 hours
Drug exposure will be measured by calculating the area under the curve (AUC) or integral of a plasma concentration-time curve. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively.
次要结局
未报告次要终点
研究者
Prakash Pandalai
Assistant Professor
University of Kentucky