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

• ClinicalTrials.gov Identifier: NCT05447715
• Recruitment Status: Not yet recruiting
• First Posted: July 7, 2022
• Last Update Posted: July 7, 2022
• Sponsor: Weijian Guo
• Information provided by (Responsible Party): Weijian Guo, Fudan University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: Fruquintinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fruquintinib Sequential BEV+FOLFIRI vs. BEV+FOLFIRI Sequential Fruquintinib in the Treatment of Metastatic Colorectal Cancer That Has Failed Previous Fluorouracil/Oxaliplatin Therapy
• Estimated Study Start Date: August 31, 2022
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: January 31, 2025

Arms and Interventions

Arm	Intervention/treatment
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
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

Outcome Measures

Primary Outcome Measures :

1. Sequential treatment of PFS with furoquitinib in second-line (F-C group) versus third-line (C-F group) [ Time Frame: 10 months ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jinjia Chang; +86-021-64175590; iamchangjinjia@163.com

Contact: Weijian Guo, MD

Locations

China, Shanghai

Fudan University Cancer Hospital

ShangHai, Shanghai, China, 200032

Contact: Weijian Guo, PHD

Sponsors and Collaborators

Weijian Guo

Investigators

• Principal Investigator: Weijian Guo, MD; Fudan University

More Information

• Responsible Party: Weijian Guo, Chief physician, Fudan University
• ClinicalTrials.gov Identifier: NCT05447715
• Other Study ID Numbers: FBIRI
• First Posted: July 7, 2022
• Last Update Posted: July 7, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Weijian Guo, Fudan University:

Metastatic Colorectal Cancer; Fruquintinib; bevacizumab (BEV); FOLFIRI; second-line treatment; third-line treatment

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases