Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine as Maintenance Therapy After First-Line Treatment in Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT05659290
• Recruitment Status: Recruiting
• First Posted: December 21, 2022
• Last Update Posted: January 6, 2023
• Sponsor: Nanfang Hospital, Southern Medical University
• Information provided by (Responsible Party): Nanfang Hospital, Southern Medical University

Study Description

Brief Summary:

This is an open-label, multicenter, randomized parallel-group phase 2 study evaluating the efficacy and safety of Fruquintinib alternating with Bevacizumab plus Capecitabine versus Bevacizumab plus Capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer. Approximately 40 patients with metastatic colorectal cancer who have achieved partial remission after completing 8 cycles of standard first-line chemotherapy (FOLFOX combined with Bevacizumab) but are still in un-resectable state will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive Fruquintinib alternating with Bevacizumab plus Capecitabine (Arm A) or Bevacizumab plus Capecitabine (Arm B). The study contains a safety lead-in phase in which the safety and efficacy of Fruquintinib alternating with Bevacizumab plus Capecitabine will be assessed in approximately 20 patients. All patients from Arm A and Arm B will be treated until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier). The study will evaluate PFS, ORR, DCR, OS and safety.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: Fruquintinib alternating with Bevacizumab plus Capecitabine; Drug: Bevacizumab plus Capecitabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Alternating Treatment With Fruquintinib and Bevacizumab Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Therapy Following First-line Treatment for Metastatic Colorectal Cancer: A Multi-center, Parallel-group, Phase II Study.
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; Efficacy of Fruquintinib alternating Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment	Drug: Fruquintinib alternating with Bevacizumab plus Capecitabine; Maintenance therapy with Fruquintinib 5mg, orally, once daily, d1-14, 2 weeks on/ 1 week off, q3w, followed by Bevacizumab 7.5 mg/kg, iv.gtt,d1,q3w + Capecitabine 850 mg/m2, orally, twice daily, d1-14, q3w; every 6 weeks as a treatment cycle; until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier).
Active Comparator: Arm B; Efficacy of Bevacizumab plus Capecitabine as maintenance therapy after first-line treatment	Drug: Bevacizumab plus Capecitabine; Maintenance therapy with Bevacizumab 7.5 mg/kg, iv.gtt,d1,q3w + Capecitabine 850 mg/m2, orally, twice daily, d1-14, q3w; every 3 weeks as a treatment cycle; until unacceptable toxicity, withdrawal of informed consent, death, or other criteria for ending the study (whichever occurs earlier).

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: 3 years ]
   Defined as the time between the onset of PD or death when a patient first receives the study drug, whichever occurs first.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 3 years ]
   Defined as the proportion of patients who achieved complete response (CR) or partial response (PR)
2. Disease Control Rate (DCR) [ Time Frame: 3 years ]
   Defined as the proportion of patients achieving CR, PR, or stable disease (SD).
3. Overall Survival (OS) [ Time Frame: 3 years ]
   Defined as the time between the patient's first receipt of the study drug to death.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Patients voluntarily participated in the study, signed the informed consent, and had good compliance;
2. Age 18-75 (including 18 and 75), gender is not limited;
3. Histologically and/or cytologically confirmed metastatic colorectal cancer (stage IV);
4. The patient with at least one measurable lesion (RECIST 1.1) achieved partial remission after 8 cycles of first-line standard chemotherapy (FOLFOX combined with bevacizumab), and the disease remained in an unresectable state.
5. ECOG performance status of 0-2 points;
6. Expected survival ≥12 weeks;
7. Blood test (without blood transfusion within 14 days) 1) Neutrophil absolute value ≥1.5×10^9/L, platelet ≥100×10^9/L, hemoglobin ≥90g/L); 2) Liver function test (aspartate aminotransferase and glutamate aminotransferase ≤3×ULN, bilirubin ≤1.5×ULN; In case of liver metastasis, AST and ALT≤5×ULN); 3) Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance (CCr)≥60ml/min);
8. Men and women of childbearing age must use effective contraceptive methods.

Exclusion Criteria:

1. Received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation, chemotherapy, immunotherapy or molecular targeted therapy for tumors within 2 weeks, and other investigational drugs;
2. Previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.;
3. A history of severe intolerance to bevacizumab and capecitabine or 5-Fu (i.e., grade 4 toxicity of one of these drugs; Class 3-4 toxicity of other co-administered drugs is not excluded);
4. Known brain or meningeal metastases:
5. Have hypertension that is not well controlled by antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
6. Obvious clinical bleeding symptoms or obvious bleeding tendency and hemoptysis within 3 months prior to treatment. Or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required;
7. Active heart disease, including myocardial infarction, severe/unstable angina in the 6 months prior to treatment. Echocardiography showed that the left ventricular ejection fraction was less than 50%, indicating poor arrhythmia control.
8. The patient had other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the previous 5 years or at the same time;
9. Known allergy to the study drug or any of its excipients;
10. Severe active infection or uncontrolled infection;
11. Any other disease, a clinically significant metabolic abnormality, abnormal physical examination or abnormal laboratory examination, for which, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for the use of the investigational agent;
12. Urine routine indicated urine protein ≥2+, and 24 hours urine protein quantity >1.0g.

Contacts and Locations

Contacts

Contact: Wangjun Liao, MD, PhD; 86-20-62787731; nfyyliaowj@163.com

Locations

China, Guangdong

Nanfang Hospital, Southern Medical University; Recruiting

Guangzhou, Guangdong, China, 510515

Contact: Wangjun Liao, MD, PhD 86-20-62787731 nfyyliaowj@163.com

Principal Investigator: Wangjun Liao, MD, PhD

Sponsors and Collaborators

Nanfang Hospital, Southern Medical University

More Information

• Responsible Party: Nanfang Hospital, Southern Medical University
• ClinicalTrials.gov Identifier: NCT05659290
• Other Study ID Numbers: NFEC-2022-479
• First Posted: December 21, 2022
• Last Update Posted: January 6, 2023
• Last Verified: December 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 Nanfang Hospital, Southern Medical University:

Metastatic Colorectal Cancer; Fruquintinib; Bevacizumab; Capecitabine; first-line treatment; Maintenance 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; Bevacizumab; Capecitabine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action