Trial Title:
Fruquintinib Plus S-1 and Raltitrexed (RSF) for mCRC
NCT ID:
NCT06427005
Condition:
Fruquintinib
S-1
Raltitrexed
Conditions: Official terms:
Tegafur
Raltitrexed
Conditions: Keywords:
S-1
Fruquintinib
raltitrexed
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib
Description:
Fruquintinib 5 mg daily for 14 days followed by a 7-day break
Arm group label:
RSF treatment arm
Other name:
Elunate
Intervention type:
Drug
Intervention name:
S-1
Description:
S-1 80-120 mg daily for 14 days, followed by a 7-day break
Arm group label:
RSF treatment arm
Other name:
Tegafur,Gimeracil and Oteracil Potassium Capsules
Intervention type:
Drug
Intervention name:
raltitrexed
Description:
raltitrexed 3 mg/m² on day 1, with a maximum dose of 5 mg
Arm group label:
RSF treatment arm
Other name:
thymidylate synthase inhibitor
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.
Detailed description:
Conducted at West China Hospital in China, this investigator-initiated, open-label,
single-arm, phase II trial included patients with mCRC that had progressed following
treatment with fluoropyrimidine, irinotecan, and oxaliplatin, and had at least one
measurable lesion. Patients could have previously received anti-EGFR (for tumors with
wild-type RAS) and anti-VEGF therapy in the first or second line, including those who had
been treated with bevacizumab in two consecutive chemotherapy regimens. 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. The primary endpoint was the ORR, while
secondary endpoints included progression-free survival (PFS), overall survival (OS), and
toxicity.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years, any gender.
2. Patients with metastatic colorectal adenocarcinoma confirmed by pathological
histology or cytology.
3. Expected survival time ≥ 12 weeks.
4. ECOG score of 0-2.
5. 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.
6. 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.
7. According to RECIST 1.1 criteria, at least one measurable tumor lesion with a
maximum diameter ≥ 1 cm as determined by spiral CT scan.
8. Laboratory test results within 1 week before enrollment must meet the following
criteria:
1. Hemoglobin ≥ 90 g/L; Platelets (PLT) ≥ 75 × 10^9/L;
2. White blood cells (WBC) ≥ 3.0 × 10^9/L; Neutrophils (ANC) ≥ 1.5 × 10^9/L;
3. Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN);
4. Total bilirubin (TBI) ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN if there is liver metastasis).
9. No prior use of raltitrexed or S-1 (or DPD enzyme inhibitors) in the treatment of
colorectal cancer.
10. Signed informed consent.
Exclusion Criteria:
1. Patients unable to take oral medications.
2. Patients who have previously been treated with small molecule TKI drugs.
3. Patients with severe hepatic or renal insufficiency, or a recent history of
myocardial infarction (within 3 months).
4. 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.
5. Patients with a history of inflammatory bowel disease or extensive colonic
resection, ≥50% or extensive small bowel resection with chronic diarrhea, or
intestinal obstruction.
6. Patients with severe uncontrolled internal medical conditions or acute infections
(fever > 38°C due to infection).
7. 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).
8. Patients with clinically significant, uncontrolled pleural effusion or ascites
despite clinical intervention.
9. Pregnant or breastfeeding women, or patients of reproductive potential (males or
females not in menopause for less than 1 year) unwilling to use contraception.
10. Patients known to be allergic to raltitrexed, S-1, and Fruquintinib or any of their
components.
11. Patients deemed unsuitable for participation in this clinical trial by the
investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sichuan University West China Hospital
Address:
City:
Chengdu
Zip:
610044
Country:
China
Status:
Recruiting
Contact:
Last name:
Weibing Leng, Ph.D
Phone:
+8618980921763
Email:
lengweibing@wchscu.cn
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Country:
China
Status:
Recruiting
Contact:
Last name:
Meng Qiu, MD
Phone:
028-85423203
Email:
qiumeng33@hotmail.com
Start date:
February 20, 2023
Completion date:
December 30, 2024
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06427005
