Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Therapy for Metastatic Colorectal Cancer After First-line Chemotherapy

• ClinicalTrials.gov Identifier: NCT05451719
• Recruitment Status: Not yet recruiting
• First Posted: July 11, 2022
• Last Update Posted: July 12, 2022
• Sponsor: Fudan University
• Information provided by (Responsible Party): Junjie Peng, Fudan University

Study Description

Brief Summary:

This is an open-label, multicenter, randomized phase 2 study evaluating the efficacy and safety of fruquintinib plus capecitabine versus capecitabine as maintenance therapy for metastatic colorectal cancer after first-line treatment. Patients who have already achieved disease control (including CR/PR and SD) after ≥6 cycles of standard first-line induction treatment, and are still unresectable would be assigned into 2 maintenance treatment groups by randomization in a 1:1 ratio to receive fruquintinib + capecitabine or capecitabine. All patients will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Colorectal Cancer Stage IV	Drug: Fruquintinib Plus Capecitabine; Drug: Capecitabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Fruquintinib Plus Capecitabine Versus Capecitabine as Maintenance Treatment for Metastatic Colorectal Cancer After First-line Chemotherapy: A Phase II, Randomized, Controlled Study
• Estimated Study Start Date: July 2022
• Estimated Primary Completion Date: July 2024
• Estimated Study Completion Date: July 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fruquintinib Plus Capecitabine; Maintenance therapy with Fruquintinib Plus Capecitabine	Drug: Fruquintinib Plus Capecitabine; Fruquintinib at the dose determined in phase safety lead-in, orally once daily, on d1-21, given every 4 weeks (Q4W). Capecitabine at the dose 850mg/m2, orally twice daily, d1-7 and d15-21, given every 4 weeks (Q4W)
Active Comparator: Capecitabine; Maintenance therapy with Capecitabine	Drug: Capecitabine; Capecitabine at the dose 850mg/m2, orally twice daily, d1-7 and d15-21, given every 4 weeks (Q4W)

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: From Baseline to primary completion date, about 24 months ]
   A duration from the date of initial treatment to disease progression or death of any cause

Secondary Outcome Measures :

1. Objective response rate (ORR, RECIST 1.1) [ Time Frame: From Baseline to primary completion date, about 24 months ]
   The incidence of confirmed complete response or partial response
2. Disease Control Rate (DCR, RECIST 1.1) [ Time Frame: From Baseline to primary completion date, about 24 months ]
   The incidence of complete response, partial response and stable disease
3. Overall survival (OS) [ Time Frame: From Baseline to primary completion date, about 24 months ]
   From the time of enrollment to death caused by any reason
4. The incidence of adverse events [ Time Frame: From Baseline to primary completion date, about 24 months ]
   The safety and tolerability of Surufatinib will be evaluated based on adverse events data.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. ≥18 years old at the time of signing the informed consent;
2. Patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
3. Patients who have achieved disease control (including CR/PR and SD) after 6 cycles of first-line standard chemotherapy and are still unresectable;
4. At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
5. ECOG performance status of 0-2;
6. Life expectancy≥3 months;
7. Adequate organ and bone marrow functions: Neutrophils >1.5×109/L, platelets >100×109/L, and hemoglobin >9 g/dL; Total bilirubin <1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <3×ULN (<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥60 mL/min; Serum creatinine < 1.5×ULN;
8. 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;
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

1. Had a surgical procedure within 4 weeks prior to treatment; Received radiation therapy, radiofrequency therapy, chemotherapy, immunotherapy or molecular targeted therapy, or other investigational drugs within 2 weeks prior to treatment;
2. Prior treatment with anti-vascular small-molecule targeted drugs, such as Fruquintinib or Regorafenib;
3. A history of severe intolerance to capecitabine or 5-FU (i.e. grade 4 toxicity of one of the drugs; Grade 3-4 toxicity of other concomitant drugs is not excluded);
4. Symptomatic brain or meningeal metastases (except for patients with BMS who have received local radiotherapy or surgery for more than 6 months and whose disease is stable).
5. Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
6. Have obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding > 30 mL within 3 months, hematemesis, black feces, hematozoia), hemoptysis (fresh blood > 5 mL within 4 weeks), etc. Treatment for venous/venous thrombosis events within the previous 6 months, such as cerebrovascular accident (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);
7. Active heart disease, including myocardial infarction, severe/unstable angina, 6 months prior to treatment. Echocardiography examination left ventricular ejection fraction < 50%, arrhythmia control is not good;
8. The patient has had other malignant tumors within 3 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
9. Allergy to the study drug or any of its excipients;
10. Severe infection with active or uncontrolled infection;
11. Any other disease, with clinical significance of metabolic abnormalities, abnormal physical examination or laboratory abnormalities, according to researchers, there is reason to suspect the patient has not suitable for the use of study drugs of a disease or condition (such as have a seizure and require treatment), or will affect the interpretation of results, or to make patients in high-risk situations;
12. Urine routine showed urine protein ≥2+, and 24-hour urine protein level >1.0g.

Contacts and Locations

Contacts

Contact: Junjie Peng, MD, PhD; 86-18017317122; pengjj67@hotmail.com

Contact: Wenhua Li, MD, PhD; 13817922257; whliiris@hotmail.com

Sponsors and Collaborators

Fudan University

More Information

• Responsible Party: Junjie Peng, Chief Physician, Fudan University
• ClinicalTrials.gov Identifier: NCT05451719
• Other Study ID Numbers: HMPL-013-FLAG-C116
• First Posted: July 11, 2022
• Last Update Posted: July 12, 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 Junjie Peng, Fudan University:

Colorectal Cancer

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; Capecitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents