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

NCT04733963 | Unknown Phase 2

• 1 other identifier: FRUCA
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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).

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer Fruquintinib maintenance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Other Outcomes (1)

• Exploratory Endpoint

  From Baseline to primary completion date, about 24 months

Study Arms (2)

Arm A

EXPERIMENTAL

Maintenance therapy with Fruquintinib Plus Capecitabine

Drug: Fruquintinib Plus Capecitabine

Arm B

ACTIVE COMPARATOR

Maintenance therapy with Bevacizumab Plus Capecitabine

Drug: Bevacizumab Plus Capecitabine

Interventions

Fruquintinib Plus Capecitabine DRUG

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

Arm A

Bevacizumab Plus Capecitabine DRUG

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

Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• LVEF≥50%;
• 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;
• 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;
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

You may not qualify if:

• 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;
• Severe intolerance to capecitabine or 5-FU;
• Disability of serious uncontrolled intercurrence infection;
• Uncontrolled hemorrhage in GI;
• Have evidence or a history of bleeding tendency within two months of the enrollment;
• Abdominal fistula or gastrointestinal perforation occurred within 6 months before the first treatment, unless repaired by surgery;

Sponsors & Collaborators

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

Study Sites (1)

the Second Affiliated Hospital of Medical College of Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

YUAN YING

CONTACT

+86-13858193601; yuanying1999@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 2, 2021
• Study Start: March 1, 2021
• Primary Completion: January 1, 2023
• Study Completion: February 1, 2023
• Last Updated: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)