Evaluating factors predicting treatment effects for advanced liver cancer

Observational Study of Factors Predicting Therapeutic Effects and Clinical Prognosis After Hepatic Artery Infusion Chemotherapy (HAIC) for Locally Advanced Hepatocellular Carcinoma (HCC)

This study is trying to find out if certain pre-surgery tests can help predict how well chemotherapy works for people with advanced liver cancer.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: lenvatinib, chemotherapy, radiation, Sorafinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05002452 on ClinicalTrials.gov

What this trial studies

This observational study aims to identify easily obtainable preoperative factors that can predict the therapeutic effects and clinical prognosis of hepatic artery infusion chemotherapy (HAIC) in patients with locally advanced hepatocellular carcinoma (HCC). Patients diagnosed with advanced HCC will receive standard HAIC treatment, and their outcomes will be monitored through routine follow-up. The study focuses on analyzing data from preoperative blood tests, imaging, and pathology to improve prognostic models for HAIC. By understanding these predictive factors, the study seeks to enhance treatment strategies for HCC patients.

Who should consider this trial

Good fit: Ideal candidates for this study are patients diagnosed with unresectable or metastatic hepatocellular carcinoma who are not suitable for other loco-regional therapies.

Not a fit: Patients with early-stage HCC or those who are candidates for curative treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment outcomes and better prognostic assessments for patients with advanced liver cancer.

How similar studies have performed: Previous studies have shown that HAIC can be beneficial for advanced HCC, but the specific predictive factors being evaluated in this study are novel.

Eligibility criteria

Inclusion Criteria:

* Written informed consent must be obtained prior to any screening procedures.
* Cytohistological confirmation is required for diagnosis of HCC.
* Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
* At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
* Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
* Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.
* Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.
* Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.
* Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:
* Hemoglobin \> 100g/L
* Absolute neutrophil count \>3.0 ×109/L
* Neutrophil count \> 1.5 ×109/L
* Platelet count ≥ 50.0 ×109/L
* Total bilirubin \< 51 μmol/L
* Alanine transaminase (ALT) and aminotransferase (AST) \< 5 x upper limit of normal
* Albumin \> 28 g/L
* Prothrombin time (PT)-international normalized ratio (INR) \< 2.3, or PT \< 6 seconds above control
* Serum creatinine \< 110 μmol/L
* Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

* Received any prior systemic chemotherapy or molecular-targeted therapy for HCC such as sorafenib, lenvatinib.
* Previous local therapy completed less than 4 weeks prior to the dosing and, if present any related acute toxicity \> grade 1.
* Any contraindications for hepatic arterial infusion procedure:
* Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).
* Renal failure / insufficiency requiring hemo-or peritoneal dialysis.
* Known severe atheromatosis.
* Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
* Patients with any other malignancies within the last 3 years before study start.
* History of HCC tumor rupture.
* Patients with severe encephalopathy.
* Patients with known active bleeding (e.g. from GI ulcers, esophageal varices) within 2 months prior to baseline/screening visit or with history or evidence of inherited bleeding diathesis or coagulopathy.
* Clinically significant (CTC grade 3 or 4) venous or arterial thrombotic disease within past 6 months.
* History of cardiac disease:
* Congestive heart failure \>New York Heart Association (NYHA) class 2 (refer to Appendix 13.9).
* Active coronary artery disease (CAD) (myocardial infarction more than 6 months prior to study entry is allowed).
* Cardiac arrhythmias (\>Grade 2 NCI-CTCAE Version 4.0) which are poorly controlled with anti-arrhythmic therapy or requiring pace maker.
* Uncontrolled blood hypertension (\> 160/100 mm/Hg).
* Serious, non-healing wound, ulcer, or bone fracture.
* History of abdominal fistula, GI perforation, or intra-abdominal abscess within past 6 months prior to study treatment.
* Clinically significant third space fluid accumulation (i.e., ascites requiring tapping despite use of diuretic or pleural effusion that either required tapping or is associated with shortness of breath).
* Patients who have undergone major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of the start of protocol treatment.
* History of a bone marrow or solid organ transplant.
* Use of biologic response modifiers, such as G-colony stimulating factor (CSF), within 3 weeks prior to start of study drug. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however, they may not be substituted for a required dose reduction). Subjects taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 1 month prior to the study or during the study.
* Any other condition that would, in the Investigator's judgment, contraindicate patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable or unwilling to swallow medication, social/ psychological issues, etc.
* Unable to undergo either contrast-enhanced magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT).
* Known history of human immunodeficiency virus (HIV) seropositivity. HIV testing is not required as part of this study.
* Patients who have received any other investigational agents within a period of time that is less than the cycle length used for that treatment or equal to 4 weeks (whichever is shorter) prior to starting study drug and recovered from any side effects to grade 1 or less.
* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

Where this trial is running

Guangzhou, Guangdong

• Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Ming Zhao, M.D. — Department of Minimally Invasive and Interventional Radiology, Liver Cancer
• Study coordinator: Ming Zhao, M.D.

Conditions: Hepatocellular Carcinoma, Arterial infusion chemotherapy, FOLFOX