Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

NCT ID: NCT05842525

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2024-12-30

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study group

Fruquintinib combined with FOLFIRI

Group Type: EXPERIMENTAL

intensive treatment

Intervention Type: DRUG

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）

Maintenance treatment

Intervention Type: DRUG

Fruquintinib 5mg, orally, once daily, 3 weeks on/ 1 week off

Interventions

intensive treatment

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

Maintenance treatment

Fruquintinib 5mg, orally, once daily, 3 weeks on/ 1 week off

Intervention Type: DRUG

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.

-

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: collaborator

Hunan Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

zhenyang Liu, MD

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Locations

Hunan Cancer hospital

Changsha, Hunan, China

Countries

China

Central Contacts

zhenyang Liu, MD PhD

Role: CONTACT

liuzhenyang@hnca.org.cn

0731-89762131

xiaolin Yang, MD

Role: CONTACT

yangxiaolin@hnca.org.cn

0731-89762131'

Facility Contacts

zhenyang Liu, MD

Role: primary

liuzhenyang@hnca.org.cn

18673181133

Other Identifiers

HNSZL-FK-01

Identifier Type: -

Identifier Source: org_study_id