PI-88 in Hepatocellular Carcinoma After Hepatectomy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of PI-88 to inhibit or reduce tumor recurrence in patients with hepatocellular carcinoma following hepatectomy.

Detailed Description
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Although early diagnosis and treatment improve survival, hepatocellular carcinoma (HCC) is rarely cured and recurs frequently after regional therapy or transplantation. Hepatic resection can improve 5-year recurrence-free survival by up to 25%. Micrometastases of HCC have been detected by molecular techniques in 88% of patients at the time of surgery, and probably cause postoperative recurrence. Efforts to reduce the risk of recurrence after a curative resection have been tried, including various regimens of adjuvant and neoadjuvant therapy. In this study , an anti-angiogenic agent, PI-88, is being used as an adjuvant therapy for HCC patients after curative hepatic resection. The efficacy endpoints, including tumour non-recurrence rate, time to first recurrence and 1-year survival rate are being evaluated. Several risk factors associated with tumour recurrence are also being analysed.

Official Title
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A Randomized, Multi-centre, Efficacy Evaluation of PI-88 in Patients With Hepatocellular Carcinoma After Hepatectomy - A Phase II Study

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: PI-88


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have voluntarily given written informed consent Age ≥ 18 years but ≤ 75 years Males or females Histological diagnosis of hepatocellular carcinoma Curative hepatectomy within the past 4-6 weeks ECOG performance status of 0 to 2 Cardiac functional capacity ≤ to class II (New York Heart Association) Patients with adequate renal, hepatic, and haematopoietic function as defined by: Serum creatinine ≤ 2.0 mg/dL Total bilirubin < 2.5 mg/dL Neutrophil count > 1.5 x 10^9/L ALT < 5 x upper limit of normal (ULN) White blood cell (WBC) count ≥ 3 x 10^9/L Platelet count ≥ 80 x 10^9/L Prothrombin time international normalized ratio (PT-INR) ≤ 1.3 (or PT-INR ≤ 1.4 but PT within normal range) Activated partial thromboplastin time (APTT) < ULN Exclusion Criteria: Patients with history of allergy and/or hypersensitivity to anticoagulants/thrombolytic agents, especially heparin. Patients with history of immune mediated thrombocytopenia, thrombotic thrombocytopenic purpura, or other platelet disease Patients with previous positive result in a heparin-induced thrombocytopenia (HIT) antibody test. Patients with any tumour metastasis. Patients with uncontrolled infection or serious infection within the past 4 weeks. Patients with myocardial infarction, stroke, or congestive heart failure within the past 3 months. Patients with history of inflammatory bowel disease, any other abnormal bleeding tendency, or patients at risk of bleeding due to open wounds or planned surgery. Patients with acute or chronic gastrointestinal bleeding within the past 1 year. Patients with a history of drug abuse or psychiatric disorder. Patients with known HIV infection or AIDS-related illness. Patients who received other investigational or anti-neoplastic medication within the past 4 weeks. Use of aspirin, aspirin-containing medications, non-steroidal anti-inflammatory drugs (except for COX-2 inhibitors), heparin, low molecular weight heparin, warfarin, anti-platelet drugs, or any other anticoagulant medications 2 weeks prior to or during the study period. Women who are pregnant or breast-feeding. Women of child-bearing potential who are not using an adequate method of contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Untreated Control<br>Untreated control arm | |
| Experimental: 160 mg PI-88/Day<br>PI-88 160 mg/day SC injection | Drug: PI-88<br>* Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks<br>|
| Experimental: 250 mg PI-88/Day<br>PI-88 250 mg/day SC injection | Drug: PI-88<br>* Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour Non-recurrence Rate | The tumor non-recurrence rate at the end of the 48-week study period | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recurrence | Time to recurrence during the 48-week study period | until confirmed tumour recurrence, or for a maximum of 48 weeks | 
| Survival Rate | Survival rate at the end of the 48-week study period | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PI-88, post resection hepatoma, adjuvant therapy, hepatectomy, hepatoma