Metastatic Colorectal Cancer (CRC)
Conditions
Keywords
RAS/BRAF-mutated
Brief summary
This study is a prospective, single-arm, multicenter exploratory clinical study aimed at evaluating the efficacy and safety of Fruquintinib combined With Serplulimab and chemotherapy as first-line treatment for RAS/BRAF-mutated unresectable advanced colorectal cancer. The study plans to enroll 80 patients with RAS/BRAF-mutated unresectable advanced metastatic colorectal cancer. After evaluation and confirmation of meeting enrollment criteria, patients will receive treatment with Fruquintinib combined With Serplulimab and chemotherapy . The primary endpoint of the study is PFS, and secondary endpoints include ORR, DCR, OS, and safety.
Interventions
DRUGSerplulimab+Fruquintinib+XELOX
combination regimen of fruquintinib, serplulimab, and XELOX for 6-8 cycles. The dosing schedule is as follows: Fruquintinib: 3 mg/day, QD, PO, daily for 21 days of each 28-day cycle Serplulimab: 4.5 mg/kg, D1, intravenous infusion, Q3W XELOX ：Oxaliplatin: 130 mg/m², intravenous infusion over 0-2 hours, D1, Q3W Capecitabine: 1000 mg/m², PO, BID, D1-14, Q3W Maintenance therapy administration: After completion of the combination therapy, subjects with a response assessment of CR, PR, or SD, , will enter the maintenance phase: Fruquintinib、Serplulimaband Capecitabine , until diseas progression, unacceptable toxicity, or voluntary withdrawal of informed consent
Sponsors
Jiangsu Cancer Institute & Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 75 years (inclusive), male or female. * Diagnosis of advanced unresectable or metastatic colorectal cancer. * Confirmed RAS/BRAF mutation by testing. * No prior systemic therapy for unresectable or metastatic colorectal cancer. (Prior adjuvant or neoadjuvant chemotherapy with one regimen is allowed if recurrence occurred ≥6 months after completion of chemotherapy.) * ECOG 0 - 1. * Adequate major organ and bone marrow function (without any blood component or cell growth factor support within 14 days before enrollment): 1. Hematology: absolute neutrophil count ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, hemoglobin ≥90 g/L. 2. International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤1.5 × ULN. 3. Liver function: total bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (≤5 × ULN in patients with liver metastases). 4. Renal function: serum creatinine ≤1.5 × ULN, and creatinine clearance (CCr) ≥50 mL/min. * Female patients of childbearing potential must have a negative serum pregnancy test within 14 days before treatment. Fertile patients (male and female) must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence) with their partners during the study and for at least 6 months after the last dose
Exclusion criteria
* \- History of hypersensitivity to any anti-angiogenic targeted agent, any component of monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs. * Untreated central nervous system (CNS) metastases. * Major surgery or severe trauma within 4 weeks prior to first study drug administration. * Current use of immunosuppressive agents, or systemic or absorbable local hormone therapy for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent), and continued use within 2 weeks before enrollment. * Presence of any active autoimmune disease or history of autoimmune disease. * History of other malignancies within the past 5 years, except for radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. * Known inherited or acquired bleeding/thrombotic tendency (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.) or currently receiving thrombolytic or anticoagulant therapy. * Currently active bleeding or significant bleeding tendency within 3 months (i.e., patients at high risk of bleeding).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Progression-Free Survival（PFS） | From enrollment to the end of treatment at 18 months | The time from the start of treatment in cancer patients to the observation of disease progression or death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Objective Response Rate（ORR） | From enrollment to the end of treatment at 18 months | CR+PR |
| Overall Survival（OS） | From enrollment to the end of treatment at 36 months | Time from enrollment to death from any cause |
| DCR | From enrollment to the end of treatment at 24 months | CR+PR+SD |
| AEs | Through study completion, an average of 30 weeks | Safety analysis will be based on data from the safety population. It will primarily involve descriptive statistical analysis, with tables describing the adverse events that occurred in this study. |
Countries
China
Contacts
CONTACTLiang'jun Zhu
Outcome results
None listed