Fruquintinib Plus S-1 and Raltitrexed (RSF) for MCRC
Fruquintinib Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: a Phase II Study
Meng Qiu
66 participants
Feb 20, 2023
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria14
- 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.
Exclusion Criteria11
- 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.
Interventions
Fruquintinib 5 mg daily for 14 days followed by a 7-day break
S-1 80-120 mg daily for 14 days, followed by a 7-day break
raltitrexed 3 mg/m² on day 1, with a maximum dose of 5 mg
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06427005