Combining Fruquintinib with FOLFIRI for RAS-mutated Metastatic Colorectal Cancer

Prospective, Single-arm, Single-center Phase Ib/II Trial on the Safety and Efficacy of Fruquintinib in Combination With FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

This study is testing if combining a new drug called Fruquintinib with a standard chemotherapy treatment can help people with RAS-mutated metastatic colorectal cancer who haven't responded to previous treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: bevacizumab, ramucirumab, chemotherapy, Fruquintinib
• Locations: 1 site (Beijing)
• Trial ID: NCT05522738 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of Fruquintinib in combination with FOLFIRI for patients with RAS-mutated metastatic colorectal cancer who have not responded to first-line treatment. It is a prospective, single-armed, single-center phase Ib/II trial conducted at the Chinese PLA General Hospital. The study aims to provide a new treatment option for this patient population, focusing on those who have failed standard therapies. Participants will be closely monitored for treatment response and safety outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with pathologically confirmed unresectable metastatic colorectal cancer and known RAS gene mutations who have failed first-line treatment.

Not a fit: Patients who have not been diagnosed with RAS mutations or those who have not failed first-line therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with RAS-mutated metastatic colorectal cancer who have limited alternatives.

How similar studies have performed: While there have been studies on RAS mutations in colorectal cancer, the specific combination of Fruquintinib and FOLFIRI in this context is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Fully understand the study and voluntarily sign the informed consent form;
2. Age ≥ 18 years;
3. Pathologically confirmed unresectable metastatic colorectal cancer;
4. Known RAS gene mutations;
5. failed standard first-line FOLFOX/XELOX combined with bevacizumab;
6. ECOG performance status 0-1;
7. BMI ≥ 18;
8. Expected survival ≥ 3 months;
9. Vital organ function meets the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment):

   * Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L;
   * Platelets ≥ 100 x 109/L;
   * Hemoglobin ≥ 90 g/L;
   * Total bilirubin TBIL ≤ 1.5 × ULN;
   * ALT and AST ≤ 5 x ULN;
   * Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 x ULN (and creatinine clearance (CCr) ≥ 50 mL/min);
   * Left ventricular ejection fraction (LVEF) \> = 50%;
   * Fridericia corrected QT interval (QTcF) \< 470 milliseconds.
   * INR ≤ 1.5 x ULN, APTT ≤ 1.5 x ULN.
10. Women of childbearing age should take effective contraceptive measures;
11. Good compliance and cooperation with follow-up.

Exclusion Criteria:

1. Unable to comply with the study protocol or study procedures;
2. Known BRAF gene mutations;
3. evidence of central nervous system metastasis, or associated with severe malignant pleural effusion and ascites;
4. Previous treatment with irinotecan;
5. previous treatment with VEGFR inhibitor
6. Concurrent use of any other investigational drug, or enrollment in a clinical trial of other investigational drug therapy within 4 weeks before enrollment;
7. Inactivated vaccines within 4 weeks before enrollment or possibly during the study;
8. patients in the study group underwent major surgery or severe traumatic injury, fracture or ulcer within 4 weeks;
9. Receiving blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment;
10. Alcohol or drug abuse within 4 weeks prior to enrollment;
11. Any factor affecting oral administration;
12. Concurrent any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
13. Uncontrollable serious concurrent infections resulting in disability;
14. Proteinuria ≥ 2 + (1.0 g/24 h)
15. Evidence or history of bleeding tendency within 2 months before enrollment, regardless of seriousness;
16. Arterial/venous thromboembolic events, such as cerebrovascular accidents (including transient ischemic attack), within 12 months before the first treatment;
17. Acute myocardial infarction, acute coronary syndrome or CABG within 6 months prior to the first treatment;
18. Fractures or wounds that have not been healed for a long time;
19. Coagulopathy, bleeding tendency, or ongoing anticoagulant therapy;
20. Patients with other malignant tumors within 5 years before enrollment, except for skin basal cell carcinoma or squamous cell carcinoma after radical resection, or cervical carcinoma in situ;
21. Active autoimmune disease or history of autoimmune disease within 4 weeks before enrollment;
22. Previous allogeneic bone marrow transplantation or organ transplantation;
23. Subjects who are allergic to the study drug or any of its excipients;
24. clinically significant electrolyte abnormalities judged by the investigator;
25. Known human immunodeficiency virus (HIV) infection. Known history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must have excluded active HBV infection, ie, positive HBV DNA (\> 1 × 104 copies/mL or \> 2000 IU/mL); known hepatitis C virus (HCV) infection and positive HCV RNA (\> 1 × 103 copies/mL);
26. Unresolved toxicities above CTCAE v5.0 grade 1 due to any prior anticancer therapy, excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2;
27. Any other diseases, clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the investigator 's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of the study drug (such as having seizures and requiring treatment), or will affect the interpretation of the study results, or put the patient at high risk;
28. Pregnant or lactating females;
29. Patients who the investigator considers inappropriate for inclusion in this study.

Where this trial is running

Beijing

• Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Guanghai Dai, Doctor — Chinese PLA General Hospital

Conditions Metastatic Colorectal Cancer; RAS-mutant; second-line