Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Therapy for Metastatic Colorectal Cancer After First-line Chemotherapy
Primary Purpose
Colorectal Cancer, Colorectal Cancer Stage IV
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Fruquintinib Plus Capecitabine
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- ≥18 years old 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 6 cycles of first-line standard chemotherapy and are still unresectable;
- At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
- ECOG performance status of 0-2;
- 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) <3×ULN (<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥60 mL/min; Serum creatinine < 1.5×ULN;
- 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.
Exclusion Criteria:
- Had a surgical procedure within 4 weeks prior to treatment; Received radiation therapy, radiofrequency therapy, chemotherapy, immunotherapy or molecular targeted therapy, or other investigational drugs within 2 weeks prior to treatment;
- Prior treatment with anti-vascular small-molecule targeted drugs, such as Fruquintinib or Regorafenib;
- A history of severe intolerance to capecitabine or 5-FU (i.e. grade 4 toxicity of one of the drugs; Grade 3-4 toxicity of other concomitant drugs is not excluded);
- Symptomatic brain or meningeal metastases (except for patients with BMS who have received local radiotherapy or surgery for more than 6 months and whose disease is stable).
- Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
- Have obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding > 30 mL within 3 months, hematemesis, black feces, hematozoia), hemoptysis (fresh blood > 5 mL within 4 weeks), etc. Treatment for venous/venous thrombosis events within the previous 6 months, such as cerebrovascular accident (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);
- Active heart disease, including myocardial infarction, severe/unstable angina, 6 months prior to treatment. Echocardiography examination left ventricular ejection fraction < 50%, arrhythmia control is not good;
- The patient has had other malignant tumors within 3 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
- Allergy to the study drug or any of its excipients;
- Severe infection with active or uncontrolled infection;
- Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to suspect the patient has not suitable for the use of study drugs of a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or to make patients in high-risk situations;
- Urine routine showed urine protein ≥2+, and 24-hour urine protein level >1.0g.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fruquintinib Plus Capecitabine
Capecitabine
Arm Description
Maintenance therapy with Fruquintinib Plus Capecitabine
Maintenance therapy with Capecitabine
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS)
A duration from the date of initial treatment to disease progression or death of any cause
Secondary Outcome Measures
Objective response rate (ORR, RECIST 1.1)
The incidence of confirmed complete response or partial response
Disease Control Rate (DCR, RECIST 1.1)
The incidence of complete response, partial response and stable disease
Overall survival (OS)
From the time of enrollment to death caused by any reason
The incidence of adverse events
The safety and tolerability of Surufatinib will be evaluated based on adverse events data.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05451719
Brief Title
Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Therapy for Metastatic Colorectal Cancer After First-line Chemotherapy
Official Title
Efficacy and Safety of Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Treatment for Metastatic Colorectal Cancer After First-line Chemotherapy: A Phase II, Randomized, Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan 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 phase 2 study evaluating the efficacy and safety of fruquintinib plus capecitabine versus capecitabine as maintenance therapy for metastatic colorectal cancer after first-line treatment. Patients who have already achieved disease control (including CR/PR and SD) after ≥6 cycles of standard first-line induction treatment, and are still unresectable would be assigned into 2 maintenance treatment groups by randomization in a 1:1 ratio to receive fruquintinib + capecitabine or capecitabine. All patients will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Colorectal Cancer Stage IV
Keywords
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
116 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fruquintinib Plus Capecitabine
Arm Type
Experimental
Arm Description
Maintenance therapy with Fruquintinib Plus Capecitabine
Arm Title
Capecitabine
Arm Type
Active Comparator
Arm Description
Maintenance therapy with Capecitabine
Intervention Type
Drug
Intervention Name(s)
Fruquintinib Plus Capecitabine
Intervention Description
Fruquintinib at the dose determined in phase safety lead-in, orally once daily, on d1-21, given every 4 weeks (Q4W). Capecitabine at the dose 850mg/m2, orally twice daily, d1-7 and d15-21, given every 4 weeks (Q4W)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine at the dose 850mg/m2, orally twice daily, d1-7 and d15-21, given every 4 weeks (Q4W)
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
A duration from the date of initial treatment to disease progression or death of any cause
Time Frame
From Baseline to primary completion date, about 24 months
Secondary Outcome Measure Information:
Title
Objective response rate (ORR, RECIST 1.1)
Description
The incidence of confirmed complete response or partial response
Time Frame
From Baseline to primary completion date, about 24 months
Title
Disease Control Rate (DCR, RECIST 1.1)
Description
The incidence of complete response, partial response and stable disease
Time Frame
From Baseline to primary completion date, about 24 months
Title
Overall survival (OS)
Description
From the time of enrollment to death caused by any reason
Time Frame
From Baseline to primary completion date, about 24 months
Title
The incidence of adverse events
Description
The safety and tolerability of Surufatinib will be evaluated based on adverse events data.
Time Frame
From Baseline to primary completion date, about 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥18 years old 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 6 cycles of first-line standard chemotherapy and are still unresectable;
At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
ECOG performance status of 0-2;
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) <3×ULN (<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥60 mL/min; Serum creatinine < 1.5×ULN;
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.
Exclusion Criteria:
Had a surgical procedure within 4 weeks prior to treatment; Received radiation therapy, radiofrequency therapy, chemotherapy, immunotherapy or molecular targeted therapy, or other investigational drugs within 2 weeks prior to treatment;
Prior treatment with anti-vascular small-molecule targeted drugs, such as Fruquintinib or Regorafenib;
A history of severe intolerance to capecitabine or 5-FU (i.e. grade 4 toxicity of one of the drugs; Grade 3-4 toxicity of other concomitant drugs is not excluded);
Symptomatic brain or meningeal metastases (except for patients with BMS who have received local radiotherapy or surgery for more than 6 months and whose disease is stable).
Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
Have obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding > 30 mL within 3 months, hematemesis, black feces, hematozoia), hemoptysis (fresh blood > 5 mL within 4 weeks), etc. Treatment for venous/venous thrombosis events within the previous 6 months, such as cerebrovascular accident (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);
Active heart disease, including myocardial infarction, severe/unstable angina, 6 months prior to treatment. Echocardiography examination left ventricular ejection fraction < 50%, arrhythmia control is not good;
The patient has had other malignant tumors within 3 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
Allergy to the study drug or any of its excipients;
Severe infection with active or uncontrolled infection;
Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to suspect the patient has not suitable for the use of study drugs of a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or to make patients in high-risk situations;
Urine routine showed urine protein ≥2+, and 24-hour urine protein level >1.0g.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Junjie Peng, MD, PhD
Phone
86-18017317122
Email
pengjj67@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wenhua Li, MD, PhD
Phone
13817922257
Email
whliiris@hotmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Therapy for Metastatic Colorectal Cancer After First-line Chemotherapy
We'll reach out to this number within 24 hrs