To evaluate the tolerance of patients with colorectal cancer to hyperthermic intraperitoneal chemotherapy with Raltitrexed, to determine the safety, tolerability, PK, and efficacy.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
The RTX-HIPEC protocol used classical 3+3 dose-escalation method with 7 dose levels (3, 4, 5, 6, 7, 8, 9 mg/m2)
Fudan University Shanghai Cancer Center
Shanghai, China
Occurrence of Dose limiting toxicity.
to determine dose-limiting toxicity
Time frame: Within 21 days post-treatment
tolerable dose
to determine maximum tolerable dose
Time frame: Up to 21 days post-treatment
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.
Time frame: Through study completion, up to 2 years
Maximum concentration (Cmax)
Time frame: Up to 48 hours after administration
Time to maximum concentration (Tmax)
Time frame: 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)
Time frame: Up to 48 hours after administration
Recurrence-free survival (RFS)
Time from RTX-HIPEC date until progression per RECIST v1.1 as assessed by the investigator at local site, or death due to any cause.
Time frame: Up to 2 years
Apparent volume of distribution (Vz/F) and clearance (CLz/F)
Time frame: Up to 48 hours after administration
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