Clinical trial NCT05842525: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Fruquintinib
RAS-mutant
second-line
Lead sponsor: Hunan Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Hutchison Medipharma Limited
First posted: 2023-05-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Histological or cytological confirmed colorectal cancer;
2. RAS mutation;
3. Expected survival \>12 weeks;
4. 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;
5. ECOG PS 0-1;
6. At least one measurable lesion (according to RECIST1.1);
7. Adequate hepatic, renal, heart, and hematologic functions;
8. Negative serum pregnancy test at screening for women of childbearing potential.

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Exclusion Criteria:

1. MSI-H / dMMR;
2. Received radiation therapy, surgical procedure, immunotherapy or other investigational drugs within 4 weeks prior to treatment ;
3. Prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc;
4. Prior treatment with an irinotecan-based chemotherapy regimen;
5. 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);
6. Severe infection (e.g., requiring intravenous antibiotics, antifungal drugs, or antiviral drugs) within 4 weeks prior to treatment;
7. Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
8. 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;
9. 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;
10. 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;
11. 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;
12. 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: assessed up to 1 year
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: assessed up to 1 year
Other outcomes:
measure: Overall survival (OS)
timeFrame: assessed up to 2 year
measure: Disease Control Rate (DCR)
timeFrame: assessed up to 1 year
Locations:
city: Changsha
country: China
facility: Hunan Cancer hospital
state: Hunan
Study officials:
affiliation: Hunan Cancer Hospital
name: zhenyang Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: