Fruquintinib Sequential BEV+FOLFIRI vs. BEV+FOLFIRI Sequential Fruquintinib in Metastatic Colorectal Cancer

Fruquintinib Sequential BEV+FOLFIRI vs. BEV+FOLFIRI Sequential Fruquintinib in the Treatment of Metastatic Colorectal Cancer That Has Failed Previous Fluorouracil/Oxaliplatin Therapy

This is a prospective, open, multicenter, randomized controlled phase II study designed to observe the difference of efficacy, adverse events and quality of life between second-line and third-line application of Fruquintinib in patients with metastatic colorectal cancer. The study will evaluate PFS, ORR, OS and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib

Detailed Description

A maximum of 134 patients with metastatic colorectal cancer who had previously failed to receive fluorouracil/oxaliplatin were included in the study. The patients were randomly divided into two groups according to the ratio of 1:1 and given different medication regiments. Stratified factors included left and right colorectal cancer, tumor RAS gene status, and first-line use of bevacizumab. Specific grouping and medication regimen are as follows:

Second-line treatment group (F-C group) : After enrollment, patients were given Fruquintinib 5 mg/d orally for 21 consecutive days with 7 days of rest, with a cycle of 28 days. Use drugs until the disease progresses or toxicity is intolerable, and then carry out third-line treatment. BEV+FOLFIRI was administered in the third line. Third-line medication until disease progression or toxicity becomes intolerable.

Third-line application group (C-F group) : After enrollment, patients were treated with BEV+FOLFIRI until disease progression or toxicity intolerance, and third-line treatment was carried out after progression. Fruquintinib was given in the third line of treatment, specifically: Fruquintinib 5 mg/d orally for 21 consecutive days, followed by 7 days of rest, with a cycle of 28 days. Third-line medication until disease progression or toxicity becomes intolerable.

• Study Type: Interventional
• Enrollment (Anticipated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinjia Chang; Phone Number: +86-021-64175590; Email: iamchangjinjia@163.com
• Study Contact Backup: Name: Weijian Guo, MD

Study Locations

• China
  • Shanghai
    • ShangHai, Shanghai, China, 200032
      • Fudan University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent;
2. Be 18 or older;
3. patients with metastatic colorectal adenocarcinoma confirmed by histopathology or cytopathology;
4. Failure of first-line oxaliplatin combined with fluorouracil (combined with or without targeted therapy);
5. With one or more measurable lesions, the longest diameter determined by spiral CT scan should be at least 10 mm, and the longest diameter determined by conventional CT scan should be at least 20 mm (efficacy evaluation criteria for solid tumors, namely RECIST criteria, version 1.1);
6. Eastern Oncology Collaboration group (ECOG) General status score 0 or 1;
7. The expected survival time is more than 3 months;

8. Hematopoietic function, liver and kidney function should meet the following criteria within 7 days before screening:

   Absolute neutrophil count ≥ 1.5x109 /L; Hemoglobin ≥ 9.0g/dL; Platelet count ≥ 80 x109 /L; Total bilirubin ≤1.5 times normal upper limit (ULN); Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x ULN; Alkaline phosphatase ≤ 3 x ULN; Serum creatinine ≤1.5 x ULN;

9. Men, women of reproductive age (postmenopausal women must have been in menopause for at least 12 months to be considered infertile), and their partners voluntarily used contraceptive methods that the investigator considered effective during treatment and for at least six months after the last study drug was taken.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be enrolled:

1. BRAF V600E mutation confirmed by histological or blood ctDNA gene test;
2. Heavy tumor load (such as liver tumor accounting for more than 50% of the liver volume, or a single tumor lesion with a diameter of more than 5 cm, or chest tightness, shortness of breath and other symptoms, lung metastasis that has affected respiratory function);
3. First-line treatment with irinotecan;
4. The patient has ascites or peritoneal metastasis;
5. Uncontrolled pleural effusion;
6. There is a risk of bleeding, such as a large surgical operation within one month or a small needle biopsy within two weeks; There was active gastrointestinal bleeding. Severe unhealed wounds; Hereditary bleeding tendency or coagulopathy.
7. History of gastrointestinal perforation or abdominal abscess within 6 months prior to enrollment.
8. Uncontrolled hypertension (systolic blood pressure & GT; 150mmHg and/or diastolic pressure > 100mmHg), clinically significant cardiovascular disease, such as symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), congestive heart failure exceeding the New York heart association (NYHA) class III or IV, stroke, or transient ischemic attack.
9. Active clinical infection;
10. Symptomatic brain or meningeal metastasis (unless the patient is treated > At 6 months, imaging results were negative within 4 weeks prior to study entry and tumor-related clinical symptoms were stable at study entry);
11. Patients whose seizures require management (e.g. steroids or antiepileptic therapy);
12. Undergoing kidney dialysis;
13. Have a history of other malignant tumors within 3 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
14. Chronic intestinal diseases, infectious intestinal diseases, intestinal obstruction;
15. Drug abuse and medical, psychological or social conditions that may interfere with patient participation in the study or influence the evaluation of the study results;
16. Any unstable condition or condition that may compromise patient safety and poor compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Fruquintinib sequential BEV+FOLFIRI	Drug: Fruquintinib; Fruquintinib sequential BEV+FOLFIRI vs. BEV+FOLFIRI sequential fruquintinib in the treatment of metastatic colorectal cancer that has failed previous fluorouracil/oxaliplatin therapy
OTHER: BEV+FOLFIRI sequential fruquintinib	Drug: Fruquintinib; Fruquintinib sequential BEV+FOLFIRI vs. BEV+FOLFIRI sequential fruquintinib in the treatment of metastatic colorectal cancer that has failed previous fluorouracil/oxaliplatin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sequential treatment of PFS with furoquitinib in second-line (F-C group) versus third-line (C-F group)	Sequential PFS is defined as: F-C group: time from randomization to disease progression or death after drug C, whichever occurred first. C-F group: time from randomization to disease progression or death after use of F drug, whichever occurred first.	10 months

Collaborators and Investigators

• Sponsor: Weijian Guo
• Investigators: Principal Investigator: Weijian Guo, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 31, 2022
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): January 31, 2025

Study Registration Dates

• First Submitted: July 3, 2022
• First Submitted That Met QC Criteria: July 3, 2022
• First Posted (ACTUAL): July 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 3, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer; Fruquintinib; second-line treatment; FOLFIRI; third-line treatment; bevacizumab (BEV)
• 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: FBIRI

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