Phase I Clinical Human Tolerability Test of Raltitrexed in Hyperthermic Intraperitoneal Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- the recommended phase II dose (RP2D)
研究概览
简要总结
To evaluate the tolerance of patients with colorectal cancer to hyperthermic intraperitoneal chemotherapy with Raltitrexed, to determine the safety, tolerability, PK, and efficacy.
详细描述
All patients with CRC-PM who underwent CRS at the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center between September 2020 and November 2024 were enrolled as part of the classical 3+3 dose-escalation phase I trial, and within a later expansion cohort. Initially, 3 patients were sequentially evaluated for DLTs at each dose level. The MTD was defined as the highest dose in cohorts where fewer than two of six evaluable patients experienced a DLT. Thereafter, additional patients were enrolled in an expansion cohort to determined the recommended phase II dose (RP2D). The RP2D was selected based on the DLT-defined MTD and the overall safety, tolerability, and supportive PK findings, and was further characterized in an expansion cohort at the candidate dose. The RTX-HIPEC protocol used the classical 3+3 dose escalation method with 7 dose levels (3, 4, 5, 6, 7, 8, 9 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18-75 (including 18 and 75), regardless of gender;
- •ECOG score ≤1;
- •Patients with colorectal adenocarcinoma/mucinous adenocarcinoma/signet ring cell carcinoma/mucinous tumor confirmed by histopathology;
- •The laboratory test results within 1 week before treatment meet the following conditions:
- •White blood cell (WBC) ≥ 4.0×109 /L;Neutrophil count (ANC) ≥ 1.8×109 /L;Platelet (PLT) ≥ 100×109/L;Hemoglobin (Hb) ≥ 80 g/L;Serum total bilirubin (TB) ≤ 1.5×ULN;Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT)≤ 2.5×ULN;Blood urea nitrogen (BUN) and blood creatinine (Cr) ≤ 1.5×ULN;
- •Patients voluntarily participate in this study, sign written informed consent, have good compliance and are willing to cooperate with the follow-up.
排除标准
- •Patients with severe complications were considered to be intolerant of postoperative chemotherapy;
- •Previous or concurrent malignancy, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin;
- •Patients with peptic ulcer, gastrointestinal dynamic obstruction, severe active bleeding of the digestive tract, and perforation of the digestive tract;
- •Those with a history of allergy to the drug components or metabolites in the program;
- •A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
- •had any heart disease, including :(1) angina;(2) Arrhythmia requiring medical treatment or clinically significant;(3) Myocardial infarction;(4) Heart failure;(5) any other heart disease deemed unfit to participate in this study by the researcher;
- •Female patients during pregnancy and lactation, female patients with fertility and positive test of baseline pregnancy or female patients of childbearing age who are unwilling to take effective contraceptive measures during the whole test period;
- •The accompanying diseases (including but not limited to hypertension, severe diabetes, active infection, thyroid disease, etc.) that, according to the judgment of the researcher, seriously endanger the safety of the patient or affect the completion of the study;
- •A past history of neurological or mental disorders, such as major depression, epilepsy, or dementia, that clearly affect study disclosure or follow-up evaluation;
- •Participate in other clinical trials within 30 days of enrollment and receive research drugs and any concomitant treatment containing research drugs;
- •Other conditions in which the investigator considers it inappropriate to participate in this study.
研究组 & 干预措施
HIPEC using Raltitrexed
干预措施: Raltitrexed (Drug)
结局指标
主要结局
the recommended phase II dose (RP2D)
时间窗: Through study completion, up to 2 years
The RP2D was selected based on the DLT-defined MTD and the overall safety, tolerability, and supportive PK findings.
Occurrence of Dose limiting toxicity.
时间窗: Within 21 days post-treatment
to determine dose-limiting toxicity
tolerable dose
时间窗: Up to 21 days post-treatment
to determine maximum tolerable dose
次要结局
- Maximum concentration (Cmax)(Up to 48 hours after administration)
- Time to maximum concentration (Tmax)(Up to 48 hours after administration)
- Area under the drug concentration-time curve from time 0 to the last measurable concentration time point (AUC0-t)(Up to 48 hours after administration)
- Recurrence-free survival (RFS)(Up to 2 years)
- Apparent volume of distribution (Vz/F) and clearance (CLz/F)(Up to 48 hours after administration)