Raltitrexed in HIPEC

Phase I Clinical Human Tolerability Test of Raltitrexed in Hyperthermic Intraperitoneal Chemotherapy

To evaluate the tolerance of patients with colorectal cancer to hyperthermic intraperitoneal chemotherapy with Raltitrexed, to determine the safety, tolerability, PK, and efficacy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; HIPEC; Raltitrexed
• Intervention / Treatment: Drug: Raltitrexed

Detailed Description

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
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 18-75 (including 18 and 75), regardless of gender;
2. ECOG score ≤1;
3. Patients with colorectal adenocarcinoma/mucinous adenocarcinoma/signet ring cell carcinoma/mucinous tumor confirmed by histopathology;

4. 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;

5. Patients voluntarily participate in this study, sign written informed consent, have good compliance and are willing to cooperate with the follow-up.

Exclusion Criteria:

1. Patients with severe complications were considered to be intolerant of postoperative chemotherapy;
2. 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;
3. Patients with peptic ulcer, gastrointestinal dynamic obstruction, severe active bleeding of the digestive tract, and perforation of the digestive tract;
4. Those with a history of allergy to the drug components or metabolites in the program;
5. A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
6. 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;
7. 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;
8. 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;
9. A past history of neurological or mental disorders, such as major depression, epilepsy, or dementia, that clearly affect study disclosure or follow-up evaluation;
10. Participate in other clinical trials within 30 days of enrollment and receive research drugs and any concomitant treatment containing research drugs;
11. Other conditions in which the investigator considers it inappropriate to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIPEC using Raltitrexed	Drug: Raltitrexed; The RTX-HIPEC protocol used classical 3+3 dose-escalation method with 7 dose levels (3, 4, 5, 6, 7, 8, 9 mg/m2); Other Names: HIPEC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerable dose	to determine maximum tolerable dose	Up to 21 days post-treatment
Occurrence of Dose limiting toxicity.	to determine dose-limiting toxicity	Within 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.	Through study completion, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Apparent volume of distribution (Vz/F) and clearance (CLz/F)		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.	Up to 2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Actual): December 28, 2024
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: HIPEC; Colorectal Cancer; Raltitrexed
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Therapeutics; Drug Therapy; Hyperthermia, Induced; Combined Modality Therapy; Chemotherapy, Adjuvant; Hyperthermic Intraperitoneal Chemotherapy; raltitrexed
• Other Study ID Numbers: HIPEC-RAL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No