The Efficacy and Safety of Fruquintinib Plus Chemotherapy as Second-line Treatment in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

The Efficacy and Safety of Fruquintinib Combined With Chemotherapy vs Bevacizumab Combined With Chemotherapy as Second-line Treatment in Patients With Metastatic Colorectal Cancer: A Prospective, Multi-center, Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05555901
• Other study ID #: FRESCO-3
• Status: Recruiting
• Phase: Phase 2
• Start date: June 18, 2023
• Est. completion date: September 2025

Study information

• Verified date: August 2023
• Source: Fudan University
• Contact: Jianmin Xu, MD
• Phone: 86-21-6404-1990
• Email: xujmin[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multi-center, randomized study evaluating the efficacy and safety of fruquintinib combined with chemotherapy vs bevacizumab combined with chemotherapy as second-line treatment in patients with metastatic colorectal cancer. Patients will receive fruquintinib+ FOLFIRI or bevacizumab+FOLFIRI as the second-line treatment. After receiving 4-6 months of second-line treatment, patients who achieve disease control will receive fruquintinib + capecitabine or bevacizumab+ capecitabine as maintenance treatment. All patients will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Aged 18-75years (inclusive);
• Body weight =40 kg;
• Histological or cytological confirmed colorectal cancer;
• Expected survival >12 weeks;
• Fail in previous first-line standard therapy, which must include a fluorouracil (5-fluorouracil or capecitabine), oxaliplatin ;
• At least one measurable lesion (according to RECIST1.1);
• Adequate hepatic, renal, heart, and hematologic functions;
• Negative serum pregnancy test at screening for women of childbearing potential.

Exclusion Criteria:

• Received radiation therapy, surgical procedure, chemotherapy, immunotherapy or molecular targeted therapy, or other investigational drugs within 4 weeks prior to treatment
• Prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc
• Prior treatment with an irinotecan-based chemotherapy regimen
• Symptomatic brain or meningeal metastases (except for patients with BMS who have received local radiotherapy or surgery for more than 6 months and whose disease is stable);
• Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg)
• Have obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding > 30 mL within 3 months, hematemesis, black feces, hematozoia), hemoptysis (fresh blood > 5 mL within 4 weeks), etc. Treatment for venous/venous thrombosis events within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin =300 mg/day or clopidogrel =75 mg/day);
• Tumor invasion of large vascular structures, such as pulmonary artery, superior vena cava or inferior vena cava, was found during screening, which was judged by the investigator to have a greater risk of bleeding;
• Active heart disease, including myocardial infarction, severe/unstable angina, 6 months prior to treatment. Echocardiography examination left ventricular ejection fraction < 50%, arrhythmia control is not good;
• The patient has had other malignant tumors within 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• Allergy to the study drug or any of its excipients;
• Severe infection with active or uncontrolled infection;
• Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to suspect the patient has not suitable for the use of study drugs of a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or to make patients in high-risk situations;
• Urine routine showed urine protein =2+, and 24-hour urine protein level >1.0g.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Fruquintinib+ chemotherapy
Second-line treatment : Fruquintinib+FOLFIRI Drug: Fruquintinib 4mg, orally, once daily, 3 weeks on/ 1 week off, q4w Drug: FOLFIRI regimen Irinotecan 180 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48-hour continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w Maintenance treatment:Fruquintinib+Capecitabine Drug: Fruquintinib 4mg, orally, once daily, 2 weeks on/ 1 week off, q3w Drug: Capecitabine 825 mg/m2, orally, twice daily, q3w
• Bevacizumab+ chemotherapy
Second-line treatment : Bevacizumab+FOLFIRI Drug: Bevacizumab 5mg/kg on day 1, q2w Drug: FOLFIRI regimen Irinotecan 180 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48-hour continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w Maintenance treatment:Bevacizumab+Capecitabine Drug: Bevacizumab 7.5mg/kg on day 1, q3w Drug: Capecitabine 825 mg/m2, orally, twice daily, q3w

Locations

Country	Name	City	State
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	the Second Affiliated Hospital of Medical College of Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Qilu Hospital of Shandong University (QLH)	Jinan	Shandong
China	The First Hospital of Putian City	Putian	Fujian
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Changhai Hospital	Shanghai	Shanghai
China	Renji hospital, Shanghai Jiaotong University	Shanghai	Shanghai
China	Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School	Shanghai	Shanghai
China	Zhongshan hosptial, Fudan University	Shanghai
China	The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital	Shijiazhuang	Hebei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Secondary	Objective response rate (ORR)	the proportion of patients with complete response or partial response, using RECIST v 1.1.	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Secondary	Disease Control Rate (DCR)	the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1.	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Secondary	Overall survival (OS)	time from randomization to death from any cause.	from randomization until death due to any cause, assessed up to 2 year