Study of Fruquintinib in Patients With Metastatic Colorectal Cancer

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Trial to Compare the Efficacy and Safety of Fruquintinib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Colorectal Cancer as 3rd or Above Therapy

Fruquintinib administered at 5mg once daily in 4 weeks treatment cycle (three weeks on and one week off) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with advanced Colorectal Cancer (CRC) in Phase Ib study.

This study is aimed to evaluate the efficacy and safety of Fruquintinib in the treatment of patients with metastatic CRC who have progressed after metastatic CRC second line or above standard chemotherapy.

This is a randomized, double-blind, placebo-controlled, multicenter Phase II clinical trial to compare the efficacy and safety of Fruquintinib plus Best Supportive Care (BSC) versus placebo plus BSC in patients with metastatic colorectal cancer who have progressed after second-line or above standard chemotherapy.

After checking eligibility criteria, subjects will be randomized into Fruquintinib plus BSC group (treatment group) or placebo plus BSC group (control group) in a ration of 2:1.

Primary Efficacy Endpoint:

Progression free survival (PFS) (According to RECIST Version 1.1).

Secondary Efficacy Endpoints:

Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS).

Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI common terminology criteria for adverse events (CTC AE) Version 4.0.

Inclusion Criteria:

• ≥ 18 and ≤ 75 years of age , with ≥ 40 Kg
• Histological or cytological confirmed metastatic colorectal cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Failed 2 or more lines of chemotherapy
• Adequate hepatic, renal, heart, and hematologic functions
• At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
• Signed and dated informed consent.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure

Exclusion Criteria:

• Pregnant or lactating women
• Any factors that influence the usage of oral administration
• Central nervous system (CNS) metastasis
• One of the following conditions: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure
• Abuse of alcohol or drugs
• Less than 4 weeks from the last clinical trial - Previous treatment with VEGFR inhibition
• Disability of serious uncontrolled intercurrence infection
• Proteinuria ≥ 2+ (1.0g/24hr)
• Evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness
• History of artery/venous thromboembolic events in 12 months, such as cerebral vascular accident (including transient ischemic attack) etc.
• History of acute myocardial infarction, acute coronary syndrome or coronary artery bypass graft (CABG) in 6 months
• Bone fracture or wounds that was not cured for a long time
• Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy