Fruquintinib Combined With mFOLFOX6/FOLFIRI in First-line Treatment for Metastatic Colorectal Cancer

Fruquintinib Combined With mFOLFOX6/FOLFIRI in First-line Treatment for Metastatic Colorectal Cancer：HCCSC C02 Trial

The purpose of this study is to evaluate the efficacy and safety of Fruquintinib Combined With mFOLFOX6/FOLFIRI as the first-line treatment of Metastatic Colorectal Cancer

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib Combined With mFOLFOX6/FOLFIRI

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fuxiang Zhou, M.D.; Phone Number: +86-027-67813155; Email: happyzhoufx@sina.com
• Study Contact Backup: Name: Wenbo Wang, M.D.; Phone Number: +86-027-67813215; Email: wangwenbo@whu.edu.cb

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hopital of Wuhan University
      • Contact: Fuxiang Zhou, M.D; Phone Number: +86-027-67813155; Email: happyzhoufx@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years, ≤75 years
2. Histologically confirmed unresectable or metastatic stage colorectal cancer
3. Known RAS activating mutation/wild type and BRAF wild type;
4. Patients have not received systematic treatment for unresectable or metastatic colorectal cancer (those who have received adjuvant or neoadjuvant chemotherapy with one regimen and relapsed more than 12 months after the end of chemotherapy can be enrolled);
5. At least one measurable disease according to RECIST 1.1 guidelines for solid tumors；
6. BMI≥18；
7. ECOG 0-1
8. Life expectancy > 12 weeks
9. Patients must have adequate organ function
10. Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration;
11. Informed consent has been signed.

Exclusion Criteria:

1. Have received other systemic anti-tumor therapies within 2 weeks before recruited(eg.chemotherapy or radiotherapy, immunotherapy, biological or hormonal therapy, or any VEGFR inhibitor treatment);
2. Known BRAF activating mutation
3. systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless of any antihypertensive drugs; Or patients need more than two antihypertensive drugs;
4. Clinically significant electrolyte abnormality;
5. Proteinuria ≥ 2+ (1.0g/24hr);
6. Patients have untreated central nervous system metastasis;
7. Patients have not recovered from all toxicities associated with prior anti-tumor therapy ,to acceptable baseline status, or a National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE v5.0) Grade of 0 or 1, except for alopecia and oxaliplatin induced neurotoxicity ≤ 2 , and the previous surgery did not recover completely;
8. Have received other systemic anti-tumor therapies within 4 weeks before recruited;
9. Clinical uncontrolled active infections, such as acute pneumonia and active hepatitis B / C (previous history of hepatitis B virus infection, whether drug controlled or not, HBV DNA ≥ 104) × Copy number or ≥ 2000 IU / ml);
10. Dysphagia or known malabsorption of drugs;
11. Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage in GI;
12. Have evidence or history of bleeding tendency within 2 months after enrollment, the researcher assessed that moderate or severe bleeding tendency was not suitable for enrollment;
13. Stroke (including transient ischemic attack) occurred within 12 months before admission;
14. Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
15. Pregnant or lactating women;
16. Allergic to fruquintinib；
17. History of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation;
18. Patients with acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before admission; Or a history of arterial thrombosis or deep venous thrombosis;
19. There are concomitant diseases (such as severe hypertension, diabetes, thyroid disease, active infection, etc.) that seriously endanger the safety of patients or affect the completion of the study, or any laboratory abnormalities that are not suitable for participating in the clinical trial according to the judgment of the researcher,
20. Serious psychological or mental disorders that may affect the compliance study;
21. Participating in other drug clinical trials within 4 weeks before recruited.

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: First-line treatment; First-line treatment: Fruquintinib Combined With mFOLFOX6/FOLFIRI for twelve cycles. Maintenance treatment: Fruquintinib and Capecitabine	Drug: Fruquintinib Combined With mFOLFOX6/FOLFIRI; Fruquintinib (3mg) will be given p.o. daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the 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	36 months
overall survival (OS)	OS is the time from enrollment to death due to any cause.	36 months
disease control rate (DCR)	DCR was defined as the percentage of participants who have a confirmed complete response（CR） or partial response（PR） or stable disease（SD） per RECIST 1.1 as assessed by investigator	36 months
adverse events (AE)	overall incidence of adverse events (AE); incidence of grade 3 or higher AE; incidence of severe adverse events (SAE); incidence of AEs leading to discontinuation of drug use; incidence of AEs leading to suspension of drug use.	36 months

Collaborators and Investigators

• Sponsor: Zhou Fuxiang
• Collaborators: Xiangya Hospital of Central South University; Henan Cancer Hospital; Hubei Cancer Hospital; Huangshi Central Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2021
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• 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: HCCSC C02

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