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Fruquintinib With mFOLFOX6/FOLFIRI as First-Line Therapy for Conversion Surgery in mCRC

Primary Purpose

Colorectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fruquintinib+mFOLFOX6/FOLFIRI
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

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

Inclusion Criteria: Provide written informed consent to participate in the study voluntarily. Male or female aged 18-75. Metastatic colorectal adenocarcinoma confirmed by histology or cytology. Have not received systematic anti-tumor therapy before; Patients who have received neoadjuvant/adjuvant therapy may be screened from the time of last chemotherapy to recurrence or progression more than 6 months. RAS/BRAF mutation status and UGT1A1*28/*6 gene polymorphism typing should be determined before enrollment. The ECOG PS score is 0 or 1. Life expectancy is at least 3 months. According to RECIST 1.1, the investigators evaluated that there were measurable lesions at baseline (according to RECIST 1.1), which could be measured if they had not received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy could also be selected as target lesions if progression was confirmed). The function of vital organs meets the following requirements (no blood component, cell growth factor correction therapy drugs are allowed within 14 days before the first use of the study drug); Absolute neutrophil count (ANC) ≥1.5×109/L Platelet ≥100×109/L; Hemoglobin ≥9g/dL; Serum albumin ≥2.5g/dL; Total bilirubin ≤1.5 × ULN; ALT and AST≤2.5 × ULN, if there is liver metastasis, ALT and AST≤5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault); Activated partial thromboplastin time (APTT) and International Normalized ratio (INR) ≤1.5 × ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin and INR within the intended therapeutic range of anticoagulants can be screened) Fertile female subjects are required to have a negative serum pregnancy test within 72 hours before the first dosing, are not breastfeeding, and use effective contraception (such as Iuds, contraceptives, or condoms) during the trial period and for at least 6 months after the last dosing of the study drug; Male subjects whose partner is a fertile woman should be surgically sterilized or agree to use effective contraception during the trial period and within 3 months after the last dose of the study drug. Sperm donation is not allowed during the study period; Exclusion Criteria: Local radiotherapy was received within 4 weeks prior to the first administration of the study drug, and adverse events due to radiotherapy have not returned to baseline levels. Participants who received palliative radiotherapy for peripheral sites (such as bone metastases) before 4 weeks may be admitted to the study, but must have recovered from any acute adverse effects; Known active central nervous system (CNS) metastases and/or cancerous meningitis. Participants who have previously received BMS may participate in treatment provided they have stable BMS and have not been treated with steroids for BMS for at least 28 days prior to study start. This exception does not include cancerous meningitis, as patients with cancerous meningitis are excluded regardless of clinical stability; Major surgery, open biopsy, or severe trauma occurred 28 days before the first medication; Previous history of allergy to fluorouracil or irinotecan; Have high blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) Subjects have poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA grade II or above heart failure; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias that remain poorly controlled without or after clinical intervention. 7. Clinically significant bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic ulcer or vasculitis, have occurred within 3 months before the first medication. 8. Arteriovenous thrombosis events occurring within 6 months before the first medication, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis and pulmonary embolism, etc. Shallow vein thrombosis can be included after being determined by the researcher. 9. There is another malignant tumor that is progressing or in need of aggressive treatment, except for non-melanoma skin cancer and cervical cancer in situ for which potential treatment has been performed. 10. In the investigator's judgment, the subject has other factors that may lead to the forced termination of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, serious abnormalities in laboratory test values, and family or social factors that may affect the subject's safety or the circumstances in which the trial data are collected.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fruquintinib+mFOLFOX6/FOLFIRI

Arm Description

Outcomes

Primary Outcome Measures

Objective Response Rate(ORR)
Objective Response Rate: The proportion of participants in the analyzed population who developed complete (CR) or partial response (PR) according to RECIST 1.1 criteria.

Secondary Outcome Measures

R0 Surgery Rate
R0 Surgery Rate: R0 corresponds to resection for cure or complete remission.
Disease Control Rate(DCR)
Disease Control Rate: The proportion of subjects in the analyzed population who achieved CR, PR, or stable disease (SD) according to RECIST 1.1 criteria.
Progression Free Survival(PFS)
Progression-Free Survival: Time from patient admission to first radiographic disease progression (RECIST 1.1 criteria) or death (whichever occurs first).
Overall Survival(OS)
Overall Survival: From the time of patient admission to the time of subject's death, at the end of the study, if the subject is still alive, the last known date of subject's survival is the deletion date.

Full Information

First Posted
August 21, 2023
Last Updated
August 23, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT06010888
Brief Title
Fruquintinib With mFOLFOX6/FOLFIRI as First-Line Therapy for Conversion Surgery in mCRC
Official Title
Fruquintinib With mFOLFOX6/FOLFIRI as First-Line Therapy for Conversion Surgery in mCRC: An Exploratory Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
March 31, 2026 (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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to learn about the efficacy and safety of Fruquintinib with mFOLFOX6/FOLFIRI in patients with mCRC. The main question it aims to answer is: The conversion surgery rate of the therapy mentioned above. The ORR, R0 surgery rate, DCR, PFS, OS, and safety will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fruquintinib+mFOLFOX6/FOLFIRI
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fruquintinib+mFOLFOX6/FOLFIRI
Intervention Description
Fruquintinib: 4mg po qd, d1-d21, q4w with mFOLFOX6/FOLFIRI (standard)
Primary Outcome Measure Information:
Title
Objective Response Rate(ORR)
Description
Objective Response Rate: The proportion of participants in the analyzed population who developed complete (CR) or partial response (PR) according to RECIST 1.1 criteria.
Time Frame
through study completion, an average of 2 year
Secondary Outcome Measure Information:
Title
R0 Surgery Rate
Description
R0 Surgery Rate: R0 corresponds to resection for cure or complete remission.
Time Frame
through study completion, an average of 2 year
Title
Disease Control Rate(DCR)
Description
Disease Control Rate: The proportion of subjects in the analyzed population who achieved CR, PR, or stable disease (SD) according to RECIST 1.1 criteria.
Time Frame
through study completion, an average of 2 year
Title
Progression Free Survival(PFS)
Description
Progression-Free Survival: Time from patient admission to first radiographic disease progression (RECIST 1.1 criteria) or death (whichever occurs first).
Time Frame
through study completion, an average of 2 year
Title
Overall Survival(OS)
Description
Overall Survival: From the time of patient admission to the time of subject's death, at the end of the study, if the subject is still alive, the last known date of subject's survival is the deletion date.
Time Frame
through study completion, an average of 2 year

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: Provide written informed consent to participate in the study voluntarily. Male or female aged 18-75. Metastatic colorectal adenocarcinoma confirmed by histology or cytology. Have not received systematic anti-tumor therapy before; Patients who have received neoadjuvant/adjuvant therapy may be screened from the time of last chemotherapy to recurrence or progression more than 6 months. RAS/BRAF mutation status and UGT1A1*28/*6 gene polymorphism typing should be determined before enrollment. The ECOG PS score is 0 or 1. Life expectancy is at least 3 months. According to RECIST 1.1, the investigators evaluated that there were measurable lesions at baseline (according to RECIST 1.1), which could be measured if they had not received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy could also be selected as target lesions if progression was confirmed). The function of vital organs meets the following requirements (no blood component, cell growth factor correction therapy drugs are allowed within 14 days before the first use of the study drug); Absolute neutrophil count (ANC) ≥1.5×109/L Platelet ≥100×109/L; Hemoglobin ≥9g/dL; Serum albumin ≥2.5g/dL; Total bilirubin ≤1.5 × ULN; ALT and AST≤2.5 × ULN, if there is liver metastasis, ALT and AST≤5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault); Activated partial thromboplastin time (APTT) and International Normalized ratio (INR) ≤1.5 × ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin and INR within the intended therapeutic range of anticoagulants can be screened) Fertile female subjects are required to have a negative serum pregnancy test within 72 hours before the first dosing, are not breastfeeding, and use effective contraception (such as Iuds, contraceptives, or condoms) during the trial period and for at least 6 months after the last dosing of the study drug; Male subjects whose partner is a fertile woman should be surgically sterilized or agree to use effective contraception during the trial period and within 3 months after the last dose of the study drug. Sperm donation is not allowed during the study period; Exclusion Criteria: Local radiotherapy was received within 4 weeks prior to the first administration of the study drug, and adverse events due to radiotherapy have not returned to baseline levels. Participants who received palliative radiotherapy for peripheral sites (such as bone metastases) before 4 weeks may be admitted to the study, but must have recovered from any acute adverse effects; Known active central nervous system (CNS) metastases and/or cancerous meningitis. Participants who have previously received BMS may participate in treatment provided they have stable BMS and have not been treated with steroids for BMS for at least 28 days prior to study start. This exception does not include cancerous meningitis, as patients with cancerous meningitis are excluded regardless of clinical stability; Major surgery, open biopsy, or severe trauma occurred 28 days before the first medication; Previous history of allergy to fluorouracil or irinotecan; Have high blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) Subjects have poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA grade II or above heart failure; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias that remain poorly controlled without or after clinical intervention. 7. Clinically significant bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic ulcer or vasculitis, have occurred within 3 months before the first medication. 8. Arteriovenous thrombosis events occurring within 6 months before the first medication, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis and pulmonary embolism, etc. Shallow vein thrombosis can be included after being determined by the researcher. 9. There is another malignant tumor that is progressing or in need of aggressive treatment, except for non-melanoma skin cancer and cervical cancer in situ for which potential treatment has been performed. 10. In the investigator's judgment, the subject has other factors that may lead to the forced termination of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, serious abnormalities in laboratory test values, and family or social factors that may affect the subject's safety or the circumstances in which the trial data are collected.
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinxiang Li, MD
Phone
Li
Email
lxx1149@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Fruquintinib With mFOLFOX6/FOLFIRI as First-Line Therapy for Conversion Surgery in mCRC

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