Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

The Efficacy and Safety of Fruquintinib Plus FOLFIRI as Second-line Treatment in RAS-mutated Metastatic Colorectal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05842525
• Other study ID #: HNSZL-FK-01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2023
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2023
• Source: Hunan Cancer Hospital
• Contact: zhenyang Liu, MD PhD
• Phone: 0731-89762131
• Email: liuzhenyang[@]hnca.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 42
• Est. completion date: December 30, 2024
• Est. primary completion date: May 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• 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)
• Maintenance treatment
Fruquintinib 5mg, orally, once daily, 3 weeks on/ 1 week off

Locations

Country	Name	City	State
China	Hunan Cancer hospital	Changsha	Hunan

Sponsors (2)

Lead Sponsor	Collaborator
Hunan Cancer Hospital	Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival (OS)	time from randomization to death from any cause.	assessed up to 2 year
Other	Disease Control Rate (DCR)	the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1	assessed up to 1 year
Primary	Objective response rate (ORR)	the proportion of patients with complete response or partial response, using RECIST v 1.1	assessed up to 1 year
Secondary	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	assessed up to 1 year