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Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
intensive treatment
Maintenance treatment
Sponsored by
Hunan Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Fruquintinib, RAS-mutant, second-line

Eligibility Criteria

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

Inclusion Criteria: Histological or cytological confirmed colorectal cancer; RAS mutation; Expected survival >12 weeks; Patients had disease progression during or within 3 months of the last dose of first-line therapy, which must include bevacizumab combined with oxaliplatin, and a fluoropyrimidine; ECOG PS 0-1; At least one measurable lesion (according to RECIST1.1); Adequate hepatic, renal, heart, and hematologic functions; Negative serum pregnancy test at screening for women of childbearing potential. - Exclusion Criteria: MSI-H / dMMR; Received radiation therapy, surgical procedure, immunotherapy or other investigational drugs within 4 weeks prior to treatment ; Prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc; Prior treatment with an irinotecan-based chemotherapy regimen; 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); Severe infection (e.g., requiring intravenous antibiotics, antifungal drugs, or antiviral drugs) within 4 weeks prior to treatment; Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Patients who had active bleeding or coagulopathy within 2 months before enrollment, had a tendency to bleed, or were receiving thrombolytic therapy and were considered by the investigator to be ineligible for enrollment; 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 5 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; The patient is unable to take the drug orally, or the patient has a condition judged by the investigator to affect the absorption of the drug; Women who are pregnant (with a positive pregnancy test before medication) or breastfeeding; Urine routine showed urine protein ≥2+, and 24-hour urine protein level >1.0g; Other conditions deemed by the investigator to be ineligible for inclusion in the study.

Sites / Locations

  • Hunan Cancer hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

study group

Arm Description

Fruquintinib combined with FOLFIRI

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
the proportion of patients with complete response or partial response, using RECIST v 1.1

Secondary Outcome Measures

Progression-Free Survival (PFS)
time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator

Full Information

First Posted
April 24, 2023
Last Updated
July 28, 2023
Sponsor
Hunan Cancer Hospital
Collaborators
Hutchison Medipharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05842525
Brief Title
Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer
Official Title
The Efficacy and Safety of Fruquintinib Plus FOLFIRI as Second-line Treatment in RAS-mutated Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
May 28, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hunan Cancer Hospital
Collaborators
Hutchison Medipharma Limited

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
RAS mutations are found in nearly half of colorectal cancer patients. However, except for G12C mutation, no driven gene targeted drug can be used. the commonly first-line used treatment regimen is bevacizumab combined with chemotherapy. Angiogenesis is an important therapeutic target in colorectal carcinoma. Fruquintinib is an oral small molecule inhibitor of VEGFR1/2/3, has approved for the third-line treatment of refractory colorectal cancer.
Detailed Description
This is a prospective ,single-center, open labeled, single-arm phase II study exploring the efficacy and safety of fruquintinib combined with FOLFIRI as second-line treatment of RAS-mutated metastatic colorectal cancer (mCRC) in patients with disease progression during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Fruquintinib, RAS-mutant, second-line

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
study group
Arm Type
Experimental
Arm Description
Fruquintinib combined with FOLFIRI
Intervention Type
Drug
Intervention Name(s)
intensive treatment
Intervention Description
Fruquintinib 4mg, orally, once daily, 3 weeks on/ 1 week off Irinotecan 150 mg/m2 LV 400 mg/m2 5-fluorouracil 400mg/m2 and a 46-48h continuous infusion 2400mg/m2 on day 1, q2w (intensive treatment up to 8 cycels)
Intervention Type
Drug
Intervention Name(s)
Maintenance treatment
Intervention Description
Fruquintinib 5mg, orally, once daily, 3 weeks on/ 1 week off
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
the proportion of patients with complete response or partial response, using RECIST v 1.1
Time Frame
assessed up to 1 year
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Time Frame
assessed up to 1 year
Other Pre-specified Outcome Measures:
Title
Overall survival (OS)
Description
time from randomization to death from any cause.
Time Frame
assessed up to 2 year
Title
Disease Control Rate (DCR)
Description
the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1
Time Frame
assessed up to 1 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: Histological or cytological confirmed colorectal cancer; RAS mutation; Expected survival >12 weeks; Patients had disease progression during or within 3 months of the last dose of first-line therapy, which must include bevacizumab combined with oxaliplatin, and a fluoropyrimidine; ECOG PS 0-1; At least one measurable lesion (according to RECIST1.1); Adequate hepatic, renal, heart, and hematologic functions; Negative serum pregnancy test at screening for women of childbearing potential. - Exclusion Criteria: MSI-H / dMMR; Received radiation therapy, surgical procedure, immunotherapy or other investigational drugs within 4 weeks prior to treatment ; Prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc; Prior treatment with an irinotecan-based chemotherapy regimen; 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); Severe infection (e.g., requiring intravenous antibiotics, antifungal drugs, or antiviral drugs) within 4 weeks prior to treatment; Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Patients who had active bleeding or coagulopathy within 2 months before enrollment, had a tendency to bleed, or were receiving thrombolytic therapy and were considered by the investigator to be ineligible for enrollment; 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 5 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; The patient is unable to take the drug orally, or the patient has a condition judged by the investigator to affect the absorption of the drug; Women who are pregnant (with a positive pregnancy test before medication) or breastfeeding; Urine routine showed urine protein ≥2+, and 24-hour urine protein level >1.0g; Other conditions deemed by the investigator to be ineligible for inclusion in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
zhenyang Liu, MD PhD
Phone
0731-89762131
Email
liuzhenyang@hnca.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
xiaolin Yang, MD
Phone
0731-89762131'
Email
yangxiaolin@hnca.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
zhenyang Liu, MD
Organizational Affiliation
Hunan Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hunan Cancer hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
zhenyang Liu, MD
Phone
18673181133
Email
liuzhenyang@hnca.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

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