A Phase II, Randomized, Controlled Study to Assess the Efficacy and Safety of Fruquintinib Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Treatment Following First-line Chemotherapy for Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Fruquintinib Plus Capecitabine
- Conditions
- Colorectal Cancer
- Sponsor
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Progression Free Survival
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an open-label, multicenter, randomized phase 2 study evaluating the efficacy and safety of fruquintinib plus capecitabine versus bevacizumab plus capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer. Patients who have already achieved disease control (including CR/PR and SD), without discontinuation for toxicity, and are progression free after 4-6 months of standard first-line induction treatment will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive fruquintinib + capecitabine (Arm A) or bevacizumab + capecitabine (Arm B). The study contains a safety lead-in phase in which the safety and tolerability of fruquintinib + capecitabine will be assessed prior to the phase 2 portion of the study. All patients from Arm A and Arm B will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal (whichever occurs earlier).
Investigators
Ying Yuan, MD
Professor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •18-75 years old (including 18 and 75) at the time of signing the informed consent;
- •Patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
- •Patients who have achieved disease control (including CR/PR and SD) after 4-6 months of first-line standard chemotherapy (FOLFOX, FOLFIRI, XELOX ± targeted therapy) and are progression free at the start of maintenance therapy;
- •At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
- •ECOG performance status of 0-1;
- •Body weight ≥40Kg;
- •Life expectancy≥3 months;
- •Adequate organ and bone marrow functions:
- •Neutrophils \>1.5×109/L, platelets \>100×109/L, and hemoglobin \>9 g/dL; Total bilirubin \<1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<2.5×ULN (\<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥50 mL/min; Urinary protein / creatinine ratio \< 1 (or urine analysis \< 1 + or 24-hour urinary protein \< 1g / 24 h);
- •Able to take oral medication;
Exclusion Criteria
- •Pregnant or lactating women;
- •Any factors that influence the usage of oral administration;
- •Those who have been proved to be allergic to fruquintinib and / or its excipients;
- •Blood transfusion was performed within 1 week before randomization;
- •Non-controlled hypertension after monotherapy, that is, systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90mmHg;
- •Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure;
- •Clinically significant electrolyte abnormality;
- •Proteinuria ≥ 2+ (1.0g/24hr);
- •Previous treatment with VEGFR inhibition;
- •Evidence of CNS metastasis;
Arms & Interventions
Arm A
Maintenance therapy with Fruquintinib Plus Capecitabine
Intervention: Fruquintinib Plus Capecitabine
Arm B
Maintenance therapy with Bevacizumab Plus Capecitabine
Intervention: Bevacizumab Plus Capecitabine
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: From Baseline to primary completion date, about 2 years
Progression-free survival is determined from the date of treatment to PD or death from any cause
Secondary Outcomes
- Overall Survival(From Baseline to primary completion date, about 2 years)
- Adverse Events and Serious Adverse Events(From Baseline to primary completion date, about 2 years)
- QoL(From Baseline to primary completion date, about 24 months)