Fruquintinib Plus S-1 and Raltitrexed (RSF) for MCRC

NCT06427005 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-71
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

Based on the FRECO-2 study, Fruquintinib has become one of the standard third-line treatments for advanced colorectal cancer; however, its objective response rate (ORR) remains low. Our previous studies have shown that the combination of raltitrexed and S-1 -/+ bevacizumab is effective and provides a significant survival benefit in patients with metastatic colorectal cancer (mCRC) who are refractory to standard treatments. This study aims to evaluate the efficacy and safety of combining Fruquintinib with S-1 and raltitrexed in these patients.

Conditions

Fruquintinib; S-1; Raltitrexed

Keywords

S-1; Fruquintinib; raltitrexed

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1

  about a year

Secondary Outcomes (3)

• DCR

  about a year

• OS

  about a year

• Safety and tolerability

  about a year

Study Arms (1)

RSF treatment arm

EXPERIMENTAL

Participants received Fruquintinib (5 mg daily for 14 days followed by a 7-day break), oral S-1 (80-120 mg daily for 14 days, followed by a 7-day break), and raltitrexed (3 mg/m² on day 1, with a maximum dose of 5 mg) every 3 weeks.

Drug: Fruquintinib; Drug: S-1; Drug: raltitrexed

Interventions

Fruquintinib DRUG

Fruquintinib 5 mg daily for 14 days followed by a 7-day break

Also known as: Elunate

RSF treatment arm

S-1 DRUG

S-1 80-120 mg daily for 14 days, followed by a 7-day break

Also known as: Tegafur,Gimeracil and Oteracil Potassium Capsules

RSF treatment arm

raltitrexed DRUG

raltitrexed 3 mg/m² on day 1, with a maximum dose of 5 mg

Also known as: thymidylate synthase inhibitor

RSF treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, any gender.
• Patients with metastatic colorectal adenocarcinoma confirmed by pathological histology or cytology.
• Expected survival time ≥ 12 weeks.
• ECOG score of 0-2.
• Previously treated for metastatic colorectal cancer with fluoropyrimidine (allowing intravenous and/or oral fluoropyrimidine formulations, excluding DPD enzyme inhibitors), irinotecan, and oxaliplatin chemotherapy, which failed (treatment failure defined as intolerable adverse reactions, disease progression during treatment, or disease progression within 6 months after completing adjuvant chemotherapy); regardless of prior use of targeted drugs such as cetuximab or bevacizumab.
• Patients must have an interval of at least 2 weeks since the last chemotherapy (at least 1 week for oral chemotherapy drugs) or more than 4 weeks since the end of radiotherapy, with the study's observable lesions located outside the radiotherapy target area.
• According to RECIST 1.1 criteria, at least one measurable tumor lesion with a maximum diameter ≥ 1 cm as determined by spiral CT scan.
• Laboratory test results within 1 week before enrollment must meet the following criteria:
• Hemoglobin ≥ 90 g/L; Platelets (PLT) ≥ 75 × 10\^9/L;
• White blood cells (WBC) ≥ 3.0 × 10\^9/L; Neutrophils (ANC) ≥ 1.5 × 10\^9/L;
• Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN);
• Total bilirubin (TBI) ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN if there is liver metastasis).
• No prior use of raltitrexed or S-1 (or DPD enzyme inhibitors) in the treatment of colorectal cancer.
• Signed informed consent.

You may not qualify if:

• Patients unable to take oral medications.
• Patients who have previously been treated with small molecule TKI drugs.
• Patients with severe hepatic or renal insufficiency, or a recent history of myocardial infarction (within 3 months).
• Patients with a history of other malignancies within the past five years, except for cured cervical carcinoma in situ and basal cell carcinoma of the skin.
• Patients with a history of inflammatory bowel disease or extensive colonic resection, ≥50% or extensive small bowel resection with chronic diarrhea, or intestinal obstruction.
• Patients with severe uncontrolled internal medical conditions or acute infections (fever \> 38°C due to infection).
• Patients with symptomatic brain or leptomeningeal metastases (unless the patient has been treated for brain or leptomeningeal metastases \> 6 months, with negative imaging results within 4 weeks before study entry, and has stable clinical symptoms related to brain or leptomeningeal metastases at study entry).
• Patients with clinically significant, uncontrolled pleural effusion or ascites despite clinical intervention.
• Pregnant or breastfeeding women, or patients of reproductive potential (males or females not in menopause for less than 1 year) unwilling to use contraception.
• Patients known to be allergic to raltitrexed, S-1, and Fruquintinib or any of their components.
• Patients deemed unsuitable for participation in this clinical trial by the investigator.

Sponsors & Collaborators

• Meng Qiu: lead
• Beijing Xisike Clinical Oncology Research Foundation: collaborator

Study Sites (2)

Sichuan University West China Hospital

Chengdu, Sichuan, 610044, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

RECRUITING

Related Publications (1)

• Leng W, Wen Z, Wang H, Cao P, Liu J, Luo D, Qiu M. Raltitrexed, S-1 and fruquintinib (RSF) in the treatment of refractory metastatic colorectal cancer: study protocol for a multicenter, prospective, single-arm, phase II trial. BMC Cancer. 2025 Feb 28;25(1):376. doi: 10.1186/s12885-025-13654-7.

  PMID: 40022044 DERIVED

MeSH Terms

Interventions

HMPL-013; S 1 (combination); Tegafur; gimeracil; potassium oxonate; raltitrexed

Intervention Hierarchy (Ancestors)

Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Meng Qiu, MD.

  Sichuan University

  STUDY DIRECTOR

Central Study Contacts

Meng Qiu, MD.

CONTACT

+8618980921776; qiumeng33@hotmail.com

Weibing C Leng, PhD.

CONTACT

+8618980921763; lengweibing@wchscu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants received Fruquintinib (5 mg daily for 14 days followed by a 7-day break), oral S-1 (80-120 mg daily for 14 days, followed by a 7-day break), and raltitrexed (3 mg/m² on day 1, with a maximum dose of 5 mg) every 3 weeks.

Study Record Dates

• First Submitted: May 19, 2024
• First Posted: May 23, 2024
• Study Start: February 20, 2023
• Primary Completion: August 18, 2025
• Study Completion: April 30, 2026
• Last Updated: January 22, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)