Fruquintinib Combined With Tislelizumab and HAIC in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Therapy

A Single-center, Single-arm, Open-label Clinical Study of Fruquintinib Combined With Tislelizumab and HAIC in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Therapy

This is a single-center, single-arm, open-label clinical study, to explore the efficacy and safety of fruquintinib combined with tislelizumab and HAIC (hepatic arterial infusion chemotherapy) in patients with colorectal liver metastases cancer (CRLM) who failed standard therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: HAIC; Drug: Fruquintinib; Drug: Tislelizumab; Drug: Raltitrexed; Drug: Oxaliplatin; Drug: Irinotecan

Detailed Description

Liver is the most common metastatic site in patients with colorectal cancer (CRC) and the leading cause of death in patients. Surgery is the best way to cure CRLM, but few patients can receive surgery, and patients prone to recurrence after surgery. It is an urgent topic to choose an effective treatment method with less side effects for CRLM patients. HAIC is a unique and effective treatment option for CRLM patients. Fruquintinib is a small molecule angiogenesis inhibitor, and has been recommended for third-line treatment of metastatic colorectal cancer (mCRC). Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, meanwhile, tislelizumab shows significant and durable antitumor activity in patients with CRC, and is well tolerated.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200062
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Informed consent has been signed
2. Histologically or cytologically confirmed unresectable advanced colorectal liver metastases cancer
3. Age ≥ 18 years, ≤75 years
4. ECOG PS：0-1
5. Expected overall survival ≥3 months
6. Patients must have at least one measurable liver metastases (RECIST 1.1)
7. Patients who have previously failed standard treatment, or who cannot tolerate standard treatment
8. Patients must have adequate organ and bone marrow function
9. 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

Exclusion Criteria:

1. Patients who are allergic or suspected to be allergic to the study drug or similar drugs
2. Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
3. Participating in other clinical trials and received at least one treatment within 4 weeks before enrollment
4. Patients with autoimmune disease or history of autoimmune disease within 4 weeks before enrollment
5. patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months
6. Patients cannot take fruquintinib orally
7. Patients who have received organ transplantation and bone marrow transplantation in the past
8. Have taken other strong inducers or inhibitors of CYP3A4, P-gp substrates and BCRP substrates within 2 weeks before the First medication
9. Received any operation (except biopsy) or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before enrollment
10. Pleural effusion or ascites causing relevant clinical symptoms, including respiratory syndrome (dyspnea≥CTC AE grade 2)
11. Clinically significant electrolyte abnormality；
12. Systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless of any antihypertensive drugs; Or patients need more than two antihypertensive drugs
13. Proteinuria ≥ 2+ (1.0g/24hr);
14. Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage in GI, or other conditions that may cause GI bleeding and perforation as determined by the investigator;
15. Have evidence or history of bleeding tendency within 3 months or thromboembolic events within 12 months before enrollment
16. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; NYHA classification > 2 Grade; ventricular arrhythmia requiring medical therapy; ECG showing QTc interval ≥ 480 ms
17. Active or uncontrolled serious infection (≥CTCAE grade 2 infection)
18. Pregnant or lactating women
19. Any other disease, with clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the judgment of investigator that the patient is not suitable for the the study drug (such as having epileptic seizures and require treatment), or would affect the interpretation of study results, or put patients at high risk
20. Clinical uncontrolled active infections, including human immunodeficiency virus (HIV) infection, active hepatitis B / C (HBV DNA Positive[1×104 copies/mL or >2000 IU/ml], HCV RNA positive[>1×103 copies/mL]);
21. Patients have other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental diseases) that require concomitant treatment, and serious laboratory abnormalities. Accompanied by family or social factors, which will affect the safety of patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: combination therapy; Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab

Procedure: HAIC; After successful percutaneous hepatic artery cannulation, superior mesenteric arteriogram and hepatic arteriogram were performed, and after confirming that the subjects were eligible for enrollment according to the results, the hepatic artery was cannulated to the predetermined position. The catheter was connected to a syringe pump in the ward for continuous pumping of drugs.; Drug: Fruquintinib; 3mg, qd, po, 21 days for a cycle, Suspend medication on the day of HAIC; Drug: Tislelizumab; 200mg, ivgtt, d1, 21 days for a cycle; Drug: Raltitrexed; 2 mg/m2, hepatic artery infusion for 15 min, d1, 4-6 Cycles; Drug: Oxaliplatin; 85 mg/m2, hepatic artery infusion for 2 h, d1, 4-6 Cycles; Drug: Irinotecan; 120mg/m2, hepatic artery perfusion for 30-90min, d1, 4-6 Cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	OS is the time from enrollment to death due to any cause.	24 months
disease control rate (DCR)	DCR was defined as the percentage of participants who have a confirmed complete response（CR） or partial response（PR） or stable disease（SD） per RECIST 1.1 as assessed by investigator	24 months
Progression-Free Survival (PFS)	PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator	24 months
Progression-Free Survival rate at 6 months	The proportion of patients who did not experience disease progression or death from treatment initiation to 6 months	6 months
Adverse events as assessed by NCI CTCAE v5.0	overall incidence of adverse events (AE); incidence of grade 3 or higher AE; incidence of severe adverse events (SAE); incidence of AEs leading to discontinuation of drug use; incidence of AEs leading to suspension of drug use	24 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Folic Acid Antagonists; Oxaliplatin; Irinotecan; Raltitrexed; Tislelizumab
• Other Study ID Numbers: HMPL-013-FLAG-C122

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No