Fruquintinib Plus FOLFIRI in RAS-mutated Metastatic Colorectal Cancer

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: intensive treatment; Drug: Maintenance treatment

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: zhenyang Liu, MD PhD; Phone Number: 0731-89762131; Email: liuzhenyang@hnca.org.cn
• Study Contact Backup: Name: xiaolin Yang, MD; Phone Number: 0731-89762131'; Email: yangxiaolin@hnca.org.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
      • Contact: zhenyang Liu, MD; Phone Number: 18673181133; Email: liuzhenyang@hnca.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study group; Fruquintinib combined with FOLFIRI	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）; Drug: Maintenance treatment; Fruquintinib 5mg, orally, once daily, 3 weeks on/ 1 week off

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	time from randomization to death from any cause.	assessed up to 2 year
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

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital
• Collaborators: Hutchison Medipharma Limited
• Investigators: Principal Investigator: zhenyang Liu, MD, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): May 28, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Fruquintinib; second-line; RAS-mutant
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: HNSZL-FK-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No