Fruquintinib Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Therapy Following First-line Treatment for Metastatic Colorectal Cancer

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

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).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib Plus Capecitabine; Drug: Bevacizumab Plus Capecitabine

• Study Type: Interventional
• Enrollment (Anticipated): 112
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YUAN YING; Phone Number: +86-13858193601; Email: yuanying1999@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Medical College of Zhejiang University
      • Contact: Ying Yuan, Ph.D & MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-75 years old (including 18 and 75) at the time of signing the informed consent;
2. Patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
3. 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;
4. At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
5. ECOG performance status of 0-1;
6. Body weight ≥40Kg;
7. LVEF≥50%;
8. Life expectancy≥3 months;

9. 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);

10. Able to take oral medication;
11. Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration;
12. 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;
3. Those who have been proved to be allergic to fruquintinib and / or its excipients;
4. Blood transfusion was performed within 1 week before randomization;
5. Non-controlled hypertension after monotherapy, that is, systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg;
6. Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure;
7. Clinically significant electrolyte abnormality;
8. Proteinuria ≥ 2+ (1.0g/24hr);
9. Previous treatment with VEGFR inhibition;
10. Evidence of CNS metastasis;
11. Severe intolerance to capecitabine or 5-FU;
12. Disability of serious uncontrolled intercurrence infection;
13. Uncontrolled hemorrhage in GI;
14. Have evidence or a history of bleeding tendency within two months of the enrollment;
15. Abdominal fistula or gastrointestinal perforation occurred within 6 months before the first treatment, unless repaired by surgery;
16. Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including stroke and transient ischemic attack) , etc.;
17. Within 6 months before the first recruitment occurs acute myocardial infarction, acute coronary syndrome or CABG;
18. Incomplete healing of skin trauma, surgical site, wound site or severe mucosal ulcer. Bone fracture or wounds that was not cured for a long time;
19. APTT and /or PT >1.5×ULN;
20. Clinically detectable secondary primary malignancies at the time of enrollment, or had other malignancies in the past 5 years (excluding fully treated basal cell carcinoma of the skin or carcinoma in situ of the cervix);
21. Patients who are not suitable for the study judged by the researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Maintenance therapy with Fruquintinib Plus Capecitabine	Drug: Fruquintinib Plus Capecitabine; Maintenance therapy with fruquintinib at the dose determined in phase safety lead-in, orally once daily, on d1-21, given every 4 weeks (Q4W); plus capecitabine at the dose 850mg/m2, orally twice daily, d1-7, given every 2 weeks (Q2W); until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal
Active Comparator: Arm B; Maintenance therapy with Bevacizumab Plus Capecitabine	Drug: Bevacizumab Plus Capecitabine; Maintenance therapy with bevacizumab at the dose 5mg/kg q2w (Q2W); plus capecitabine at the dose 850mg/m2, orally twice daily, d1-7, given every 2 weeks (Q2W); until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression-free survival is determined from the date of treatment to PD or death from any cause	From Baseline to primary completion date, about 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is determined from the date of treatment to death from any cause or the last follow-up date	From Baseline to primary completion date, about 2 years
Adverse Events and Serious Adverse Events	Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.	From Baseline to primary completion date, about 2 years
QoL	Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, Tumor Assessment Visit and End of Treatment visit.	From Baseline to primary completion date, about 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint	Explore any correlation between clinical outcomes and baseline characteristics, and biomarkers associated with the antitumor activity of fruquintinib based on blood samples	From Baseline to primary completion date, about 24 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Cancer Fruquintinib maintenance
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Bevacizumab
• Other Study ID Numbers: FRUCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No