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

NCT05435313 | Unknown Phase 2

• 1 other identifier: HMPL-013-FLAG-C122
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• disease control rate (DCR)

  24 months

• Progression-Free Survival (PFS)

  24 months

• Progression-Free Survival rate at 6 months

  6 months

• overall survival (OS)

  24 months

• Adverse events as assessed by NCI CTCAE v5.0

  24 months

Study Arms (1)

combination therapy

EXPERIMENTAL

Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab

Procedure: HAIC; Drug: Fruquintinib; Drug: Tislelizumab; Drug: Raltitrexed; Drug: Oxaliplatin; Drug: Irinotecan

Interventions

HAIC PROCEDURE

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.

combination therapy

Fruquintinib DRUG

3mg, qd, po, 21 days for a cycle, Suspend medication on the day of HAIC

combination therapy

Tislelizumab DRUG

200mg, ivgtt, d1, 21 days for a cycle

combination therapy

Raltitrexed DRUG

2 mg/m2, hepatic artery infusion for 15 min, d1, 4-6 Cycles

combination therapy

Oxaliplatin DRUG

85 mg/m2, hepatic artery infusion for 2 h, d1, 4-6 Cycles

combination therapy

Irinotecan DRUG

120mg/m2, hepatic artery perfusion for 30-90min, d1, 4-6 Cycles

combination therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients who are allergic or suspected to be allergic to the study drug or similar drugs
• 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);
• Participating in other clinical trials and received at least one treatment within 4 weeks before enrollment
• Patients with autoimmune disease or history of autoimmune disease within 4 weeks before enrollment
• patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months
• Patients cannot take fruquintinib orally
• Patients who have received organ transplantation and bone marrow transplantation in the past
• Have taken other strong inducers or inhibitors of CYP3A4, P-gp substrates and BCRP substrates within 2 weeks before the First medication
• Received any operation (except biopsy) or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before enrollment
• Pleural effusion or ascites causing relevant clinical symptoms, including respiratory syndrome (dyspnea≥CTC AE grade 2)
• Clinically significant electrolyte abnormality；
• Systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90mmHg regardless of any antihypertensive drugs; Or patients need more than two antihypertensive drugs
• Proteinuria ≥ 2+ (1.0g/24hr);
• 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;
• Have evidence or history of bleeding tendency within 3 months or thromboembolic events within 12 months before enrollment

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200062, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; tislelizumab; raltitrexed; Oxaliplatin; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of liver surgery department

Study Record Dates

• First Submitted: June 23, 2022
• First Posted: June 28, 2022
• Study Start: July 12, 2022
• Primary Completion: January 1, 2024
• Study Completion: February 1, 2024
• Last Updated: January 17, 2024

Record last verified: 2024-01

Locations

CN (1)