Efficacy of Modified Fruquintinib in Colorectal Cancer Liver Metastases: A Phase II Study

• ClinicalTrials.gov Identifier: NCT06018714
• Recruitment Status: Recruiting
• First Posted: August 31, 2023
• Last Update Posted: August 31, 2023
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): ZHI-ZHONG PAN, Sun Yat-sen University

Tracking Information

• First Submitted Date: August 9, 2023
• First Posted Date: August 31, 2023
• Last Update Posted Date: August 31, 2023
• Actual Study Start Date: May 1, 2023
• Estimated Primary Completion Date: August 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2023)

2-year recurrence and metastasis rate [ Time Frame: 2 years after NED ]

To evaluate the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy, with the 2-year recurrence and metastasis rate as the primary indicator.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 28, 2023)

2-year disease-free survival rate [ Time Frame: 2 years after NED ]

To evaluate 2-year recurrence-free survival rate, 2-year overall survival rate, recurrence-free survival period in patients accepting fruquintinib maintenance therapy.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 28, 2023)

completion rate of maintenance therapy [ Time Frame: 2 years after NED ]

To evaluate safety and completion rate of maintenance therapy

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Efficacy of Modified Fruquintinib in Colorectal Cancer Liver Metastases: A Phase II Study
• Official Title: The Clinical Efficacy of Modified Fruquintinib as Maintenance Treatment for Colorectal Cancer Liver Metastases After NED: Phase II Single-arm Prospective Study
• Brief Summary: The overall 5-year survival rate for patients with colorectal liver metastases (CRLM) is still less than 20%. Surgery-based local treatment can achieve no evidence of disease (NED) in CRLM patients, but over 60% of patients experience recurrence even after achieving NED. Even with adjuvant therapy for the 6-month perioperative period after achieving NED, the recurrence rate remains high. Fruquintinib is a selective anti-angiogenic inhibitor that may help reduce tumor recurrence and prolong the time to recurrence and metastasis. The Chinese Society of Clinical Oncology (CSCO) guidelines have recommended fruquintinib as a third-line therapy for colorectal cancer. This study aims to evaluate the effectiveness and safety of fruquintinib as a maintenance therapy for patients with advanced colorectal cancer (CRC) who have achieved no evidence of disease (NED) after completing adjuvant chemotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is a prospective, single-arm, phase II study aimed at exploring the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy. Patients will receive full supportive care while on this study.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Colorectal Cancer Metastatic

Intervention

Drug: Fruquintinib

Drug:

Maintenance treatment regimen:

Fruquintinib 5 mg, qd, po, with three weeks of continuous treatment followed by one week of drug discontinuation. Each treatment cycle lasts four weeks. The treatment will be continued for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.

Adverse drug reactions that occur during the trial will be graded according to the NCI CTCAE version 5.0 and dose adjustments will be made according to the corresponding rules.

Study Arms

Experimental: Fruquintinib group

Patients will receive Fruquintinib maintenance treatment for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.

After achieving no evidence of disease (NED), a chest, abdomen, and pelvic CT scan with contrast or a chest CT scan with abdominal and pelvic MRI scan will be performed every 6 months within 2 years. Colonoscopy will be performed annually. CEA, CA19-9, and abdominal and pelvic ultrasound will be performed every 3 months. If abnormalities are found, further imaging studies and colonoscopy will be conducted, and if necessary, a PET/CT scan will be performed.

Intervention: Drug: Fruquintinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 28, 2023): 64
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2026
• Estimated Primary Completion Date: August 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. . The pathological diagnosis was colorectal adenocarcinoma liver metastasis；
2. . Age: 18 to 75 years old,allgenders；
3. . Patients who have previously received first-line chemotherapy and have achieved disease control (PR+SD) according to RECIST 1.1;
4. . Patients with liver metastasis of colorectal cancer who have undergone curative local treatment (surgery, ablation, SBRT) and achieved no evidence of disease (NED). Definition of NED: a. After local treatment, no residual signs of primary or metastatic tumors are observed on CT, MRI, PET-CT imaging, or b. No cancer cells are found in biopsies of suspicious lesions；
5. .Completed adjuvant chemotherapy after achieving NED (e.g. 4-8 cycles of CapOX regimen, 6-12 cycles of FOLFOX regimen, or without receiving adjuvant chemotherapy recently) and evaluated as no disease progression. Last chemotherapy within 2 months from enrollment.
6. . The time interval between the last chemotherapy and enrollment does not exceed 2 months;
7. . Performance status (ECOG score) ≤ 2
8. . Hematology: WBC > 3 × 10^9 / L; PLT > 80 × 10^9 / L; Hb > 90 g/L;
9. . Liver function: ALT and AST ≤ 2.5 × ULN; bilirubin ≤ 1.5 × ULN;
10. .Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;
11. .Signed informed consent, willingness to undergo treatment according to this protocol, and good compliance with medication.

Exclusion Criteria:

1. .Patients with tumor progression before enrollment following the completion of chemotherapy.
2. .Intestinal obstruction or incomplete intestinal obstruction.
3. .Co-existing with other serious illnesses, including severe electrolyte disorders, bleeding tendencies, etc.
4. .Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV) infection. b) Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×104 copies/mL or >2000 IU/mL)]. c) Known hepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies/mL), or other hepatitis, liver cirrhosis.
5. .Women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures.
6. .Patients with severe brain disorders or mental illnesses (such as depression, mania, obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability to self-report.
7. .Patients with autoimmune diseases, blood system disorders, and a history of organ transplantation, long-term use of steroids, or immunosuppressive agents.
8. .History of other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
9. .History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation).
10. .Known or suspected allergies to the investigational drug fruquintinib.
11. .Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
12. .Active cardiac disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina pectoris. Left ventricular ejection fraction <50% on echocardiography, poorly controlled arrhythmias.
13. .Urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification >1.0g.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Junzhong Lin, Doctor; 020-87343533; linjzh@sysucc.org.cn

Contact: Zhizhong Pan, Prof; 020-87343533; panzhzh@sysucc.org.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT06018714
• Other Study ID Numbers: 2023-FXY-096-Department of CRC
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ZHI-ZHONG PAN, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sun Yat-sen University
• Verification Date: August 2023