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Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine as Maintenance Therapy After First-Line Treatment in Metastatic Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fruquintinib alternating with Bevacizumab plus Capecitabine
Bevacizumab plus Capecitabine
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer, Fruquintinib, Bevacizumab, Capecitabine, first-line treatment, Maintenance treatment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients voluntarily participated in the study, signed the informed consent, and had good compliance; Age 18-75 (including 18 and 75), gender is not limited; Histologically and/or cytologically confirmed metastatic colorectal cancer (stage IV); The patient with at least one measurable lesion (RECIST 1.1) achieved partial remission after 8 cycles of first-line standard chemotherapy (FOLFOX combined with bevacizumab), and the disease remained in an unresectable state. ECOG performance status of 0-2 points; Expected survival ≥12 weeks; Blood test (without blood transfusion within 14 days) 1) Neutrophil absolute value ≥1.5×10^9/L, platelet ≥100×10^9/L, hemoglobin ≥90g/L); 2) Liver function test (aspartate aminotransferase and glutamate aminotransferase ≤3×ULN, bilirubin ≤1.5×ULN; In case of liver metastasis, AST and ALT≤5×ULN); 3) Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance (CCr)≥60ml/min); Men and women of childbearing age must use effective contraceptive methods. Exclusion Criteria: Received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation, chemotherapy, immunotherapy or molecular targeted therapy for tumors within 2 weeks, and other investigational drugs; Previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.; A history of severe intolerance to bevacizumab and capecitabine or 5-Fu (i.e., grade 4 toxicity of one of these drugs; Class 3-4 toxicity of other co-administered drugs is not excluded); Known brain or meningeal metastases: Have hypertension that is not well controlled by antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Obvious clinical bleeding symptoms or obvious bleeding tendency and hemoptysis within 3 months prior to treatment. Or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (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) is required; Active heart disease, including myocardial infarction, severe/unstable angina in the 6 months prior to treatment. Echocardiography showed that the left ventricular ejection fraction was less than 50%, indicating poor arrhythmia control. The patient had other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the previous 5 years or at the same time; Known allergy to the study drug or any of its excipients; Severe active infection or uncontrolled infection; Any other disease, a clinically significant metabolic abnormality, abnormal physical examination or abnormal laboratory examination, for which, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for the use of the investigational agent; Urine routine indicated urine protein ≥2+, and 24 hours urine protein quantity >1.0g.

Sites / Locations

  • Nanfang Hospital, Southern Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Efficacy of Fruquintinib alternating Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment

Efficacy of Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
Defined as the time between the onset of PD or death when a patient first receives the study drug, whichever occurs first.

Secondary Outcome Measures

Objective Response Rate (ORR)
Defined as the proportion of patients who achieved complete response (CR) or partial response (PR)
Disease Control Rate (DCR)
Defined as the proportion of patients achieving CR, PR, or stable disease (SD).
Overall Survival (OS)
Defined as the time between the patient's first receipt of the study drug to death.

Full Information

First Posted
December 13, 2022
Last Updated
January 4, 2023
Sponsor
Nanfang Hospital, Southern Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05659290
Brief Title
Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine as Maintenance Therapy After First-Line Treatment in Metastatic Colorectal Cancer
Official Title
Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Therapy Following First-line Treatment for Metastatic Colorectal Cancer: A Multi-center, Parallel-group, Phase II Study.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanfang Hospital, Southern Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open-label, multicenter, randomized parallel-group phase 2 study evaluating the efficacy and safety of Fruquintinib alternating with Bevacizumab plus Capecitabine versus Bevacizumab plus Capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer. Approximately 40 patients with metastatic colorectal cancer who have achieved partial remission after completing 8 cycles of standard first-line chemotherapy (FOLFOX combined with Bevacizumab) but are still in un-resectable state will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive Fruquintinib alternating with Bevacizumab plus Capecitabine (Arm A) or Bevacizumab plus Capecitabine (Arm B). The study contains a safety lead-in phase in which the safety and efficacy of Fruquintinib alternating with Bevacizumab plus Capecitabine will be assessed in approximately 20 patients. All patients from Arm A and Arm B will be treated until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier). The study will evaluate PFS, ORR, DCR, OS and safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic Colorectal Cancer, Fruquintinib, Bevacizumab, Capecitabine, first-line treatment, Maintenance treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Efficacy of Fruquintinib alternating Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Efficacy of Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment
Intervention Type
Drug
Intervention Name(s)
Fruquintinib alternating with Bevacizumab plus Capecitabine
Intervention Description
Maintenance therapy with Fruquintinib 5mg, orally, once daily, d1-14, 2 weeks on/ 1 week off, q3w, followed by Bevacizumab 7.5 mg/kg, iv.gtt,d1,q3w + Capecitabine 850 mg/m2, orally, twice daily, d1-14, q3w; every 6 weeks as a treatment cycle; until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier).
Intervention Type
Drug
Intervention Name(s)
Bevacizumab plus Capecitabine
Intervention Description
Maintenance therapy with Bevacizumab 7.5 mg/kg, iv.gtt,d1,q3w + Capecitabine 850 mg/m2, orally, twice daily, d1-14, q3w; every 3 weeks as a treatment cycle; until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier).
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Defined as the time between the onset of PD or death when a patient first receives the study drug, whichever occurs first.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Defined as the proportion of patients who achieved complete response (CR) or partial response (PR)
Time Frame
3 years
Title
Disease Control Rate (DCR)
Description
Defined as the proportion of patients achieving CR, PR, or stable disease (SD).
Time Frame
3 years
Title
Overall Survival (OS)
Description
Defined as the time between the patient's first receipt of the study drug to death.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients voluntarily participated in the study, signed the informed consent, and had good compliance; Age 18-75 (including 18 and 75), gender is not limited; Histologically and/or cytologically confirmed metastatic colorectal cancer (stage IV); The patient with at least one measurable lesion (RECIST 1.1) achieved partial remission after 8 cycles of first-line standard chemotherapy (FOLFOX combined with bevacizumab), and the disease remained in an unresectable state. ECOG performance status of 0-2 points; Expected survival ≥12 weeks; Blood test (without blood transfusion within 14 days) 1) Neutrophil absolute value ≥1.5×10^9/L, platelet ≥100×10^9/L, hemoglobin ≥90g/L); 2) Liver function test (aspartate aminotransferase and glutamate aminotransferase ≤3×ULN, bilirubin ≤1.5×ULN; In case of liver metastasis, AST and ALT≤5×ULN); 3) Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance (CCr)≥60ml/min); Men and women of childbearing age must use effective contraceptive methods. Exclusion Criteria: Received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation, chemotherapy, immunotherapy or molecular targeted therapy for tumors within 2 weeks, and other investigational drugs; Previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.; A history of severe intolerance to bevacizumab and capecitabine or 5-Fu (i.e., grade 4 toxicity of one of these drugs; Class 3-4 toxicity of other co-administered drugs is not excluded); Known brain or meningeal metastases: Have hypertension that is not well controlled by antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Obvious clinical bleeding symptoms or obvious bleeding tendency and hemoptysis within 3 months prior to treatment. Or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (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) is required; Active heart disease, including myocardial infarction, severe/unstable angina in the 6 months prior to treatment. Echocardiography showed that the left ventricular ejection fraction was less than 50%, indicating poor arrhythmia control. The patient had other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the previous 5 years or at the same time; Known allergy to the study drug or any of its excipients; Severe active infection or uncontrolled infection; Any other disease, a clinically significant metabolic abnormality, abnormal physical examination or abnormal laboratory examination, for which, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for the use of the investigational agent; Urine routine indicated urine protein ≥2+, and 24 hours urine protein quantity >1.0g.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wangjun Liao, MD, PhD
Phone
86-20-62787731
Email
nfyyliaowj@163.com
Facility Information:
Facility Name
Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wangjun Liao, MD, PhD
Phone
86-20-62787731
Email
nfyyliaowj@163.com
First Name & Middle Initial & Last Name & Degree
Wangjun Liao, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine as Maintenance Therapy After First-Line Treatment in Metastatic Colorectal Cancer

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