The Safety and Efficacy of HAIC+Tislelizumab+Regorafenib in Patients With Colorectal Liver Metastases

NCT05877001 | Unknown Phase 2

• 1 other identifier: 2022KT98
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Tislelizumab is an anti-PD-1 monoclonal antibody with high binding affinity for PD-1 and with minimized Fcγ receptor binding on macrophages. Regorafenib has been approved in mCRC by CFDA. Hepatic arterial infusion chemotherapy has a high local control rate for liver metastases. NCCN guidelines and several expert consensus recommend that regional hepatic arterial infusion chemotherapy can be considered as a "rescue treatment" for patients with colorectal cancer liver metastases who fail to receive first-line or second-line systemic chemotherapy, which can significantly prolong the overall survival of patients.

Conditions

Colorectal Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Safety profiles by NCI-CTCAE version 5 .0

  The evaluation of adverse events , using NCI-CTCAE version 5.0.

  From the first patient enrolled to 15 months after the last patient enrolled.

Secondary Outcomes (8)

• Overall response rate(ORR)

  up to 2 years

• Disease control rate(DCR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 2 years

• Response rate of intrahepatic lesions

  Up to 2 years

• Response rate of extrahepatic lesions

  Up to 2 years

Study Arms (1)

HAIC combined with Tislelizumab and Regorafenib

EXPERIMENTAL

HAIC combined with Tislelizumab and Regorafenib until progression or death.

Drug: Tislelizumab; Drug: Regorafenib; Other: HAIC

Interventions

Tislelizumab DRUG

200mg, IV, Q3W

Also known as: BGB-A317

HAIC combined with Tislelizumab and Regorafenib

Regorafenib DRUG

80 mg once daily for the first 3 weeks of each 4-week cycle

Also known as: BAY73-4506

HAIC combined with Tislelizumab and Regorafenib

HAIC OTHER

OXA 85mg/m2 IA 0-4h +5-Fu 2000mg/m2 IA 4-48h，CF 200mg/m2 IV 2-4h， Q3W

HAIC combined with Tislelizumab and Regorafenib

Eligibility Criteria

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

You may qualify if:

• Age≥18 years old
• Histologically or cytologically confirmed colorectal cancer with unresectable or surgical contraindicated liver metastases
• Extrahepatic metastases are allowed and the primary tumor load is assessed to be intrahepatic by two or more attending physicians
• Whether liver metastases can be resected or not is determined by two or more attending physicians according to the Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases
• Patients with unresectable colorectal liver metastases after failed standard second-line therapy
• Including, but not limited to, Oxaliplatin, Fluorouracil, and Irinotecan
• Treatment failure is defined as disease progression and intolerable toxicity
• Patients who withdrew from standard therapy due to unacceptable toxicity, guaranteed to discontinue treatment before disease progression and excluded treatment with the same drug, are also allowed to be included in the study.
• At least one measurable lesion according to RECIST 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Subject life expectancy ≥12 weeks
• Laboratory tests of bone marrow, hepatic and renal function and coagulation function within 7 days before the first dose of medication meet the study requirements
• \- No blood transfusion, blood products, or correction with granulocyte colony-stimulating factor or other hematopoietic stimulating factor within 7 days before laboratory testing.
• Female patients of childbearing age must have a negative blood pregnancy test within 7 days before the first dose of medication and male or female patients of childbearing age volunteered to take effective contraceptive measures during the whole treatment and within 3 months after treatment
• All patients must sign an informed consent form and follow the trial treatment protocol and follow up plan

You may not qualify if:

• ANC \<1.5×109/L, or platelet count \<80×109/L, or HGB \< 9g/dL;
• \- Blood transfusion to meet enrollment criteria within 2 weeks before enrollment is not allowed
• serum total bilirubin\>2.0 times upper limit of normal
• AST and/or ALT\>5.0 times upper limit of normal
• Serum creatinine\>1.5 times upper limit of normal, or creatinine clearance rate\<50ml/min(calculated according to the Cockcroft-Gault formula)
• APTT or PT\>1.5 times upper limit of normal
• Clinically significant severe electrolyte abnormalities by the investigator
• Urine protein test 2+ or more, or 24 hours urine protein quantitation ≥1.0g/24h
• Hypertension that is not stably controlled by medications: systolic blood pressure(SBP) \>140mmHg or diastolic blood pressure(DBP) \> 90mmHg
• Patients with active gastric and duodenal ulcer, ulcerative colitis or other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigators; Or patients with previous gastrointestinal perforation or gastrointestinal fistula, which is not cured after surgical treatment
• History of arterial or deep-vein thrombosis within 6 months before enrollment or evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity
• History of troke or transient ischemic attack within 12 months before enrollment
• History of heart disease within 6 months before enrollment, manifested as congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting; impaired cardiac function in NYHA class 2 or above; left ventricular ejection fraction (LVEF) \<50%
• Uncontrolled malignant pleural, ascites, or pericardial effusion
• \- defined as not being effectively controlled with diuretics or punctures

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (2)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

MeSH Terms

Interventions

tislelizumab; regorafenib

Study Officials

• Xu Zhu, MD

  Peking University Cancer Hospital & Institute

  STUDY CHAIR

Central Study Contacts

Xu Zhu, MD

CONTACT

+86-10-88196001; drzhuxu@163.com

Feng Aiwei, MD

CONTACT

+86-10-88196330; ivyfeng_1026@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: May 26, 2023
• Study Start: May 30, 2023
• Primary Completion: July 30, 2024
• Study Completion: March 1, 2025
• Last Updated: May 26, 2023

Record last verified: 2022-12

Locations

CN (2)