Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

Phase 2

Recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: fruquintinib plus TAS-102

• Registration Number: NCT05004831
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This phase II study aims to explore the efficacy and safety of fruquintinib combined with TAS-102 in the third-line treatment of patients with advanced metastatic colorectal cancer.

Detailed Description

This is a prospective, single center, one-arm phase II study. A total of 54 advanced mCRC patients refractory to standard therapies will be enrolled and administered with fruquintinib (4mg/d, qd po, D1-21, Q4W) combined with TAS-102 (70mg/m2/d, bid po, D1-5, 8-12, Q4W) until intolerable toxicity, disease progression or death. Primary endpoint of this study is PFS and secondary endpoints are OS, ORR, DCR and safety.

Study Timeline

• Study First Submitted: 2021-08-06
• Study First Submitted QC: 2021-08-06
• Study First Posted: 2021-08-13
• Study Start: 2022-03-11
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-17
• Last Update Posted: 2022-08-18
• Primary Completion: 2023-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1. ≥ 18 and ≤ 75 years of age;
2. Histological or cytological confirmed advanced metastatic colorectal cancer;
3. Refractory to at least second line standard treatment containing fluorouracil, oxaliplatin and irinotecan;
4. At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan or 20mm by conventional CT scan);
5. ECOG performance status of 0-1;
6. Life expectancy ≥ 12 weeks;
7. No previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor (TKI);
8. Signed and dated informed consent;
9. Adequate hepatic, renal, heart, and hematologic functions;
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria

1. Pregnant or lactating women;
2. Any factors that influence the usage of oral administration or any disease or condition that affects drug absorption;
3. Previous treatment with TAS-102;
4. Participated in clinical trials of other drugs within four weeks before enrollment;
5. Received other systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy;
6. International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN;
7. Clinically significant electrolyte abnormalities;
8. Subjected with hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
9. Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previous anti-cancer treatment;
10. Incomplete healing of skin wound, surgical site, traumatic site, severe mucosal ulcer or fracture;
11. Conditions that may cause gastrointestinal bleeding and perforation determined by the researcher;
12. History of arterial thrombosis or deep venous thrombosis within 6 months before enrollment;
13. Stroke and / or transient cerebral ischemia occurred within 12 months before enrollment;
14. Cardiovascular diseases with significant clinical significance;
15. LVEF<50%;
16. Congestive heart failure New York Heart Association (NYHA) grade > 2;
17. Evidence of CNS metastasis;
18. Previous treatment with VEGFR inhibition;
19. Ventricular arrhythmias requiring drug treatment;
20. Proteinuria ≥ 2+ (1.0g/24hr);
21. Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy;
22. Other malignant tumors in the past 5 years, except skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
23. Active infection that is not controlled clinically, such as acute pneumonia, active hepatitis B or hepatitis C;
24. By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
fruquintinib plus TAS-102	fruquintinib plus TAS-102	fruquintinib plus TAS-102, orally given, Q4W

Primary Outcome Measures

Name	Time	Method
PFS	from randomization up to progressive disease or EOT due to any cause, up to 2 years	Progression-free Survival

Secondary Outcome Measures

Name	Time	Method
Safety and tolerance	from first dose to within 30 days after the last dose	Safety and tolerance evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0
DCR	from randomization up to progressive disease or EOT due to any cause, up to 2 years	Disease Control Rate
ORR	from randomization up to progressive disease or EOT due to any cause, up to 2 years	Objective Response Rate
OS	from randomization until death due to any cause, assessed up to 3 years	Overall Survival

Trial Locations

Locations (1)

the first affiliated hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China