PI-88 in Hepatocellular Carcinoma After Hepatectomy

NCT ID: NCT00247728

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 172 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2008-06-30

Brief Summary

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

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Untreated Control

Untreated control arm

Group Type: NO_INTERVENTION

No interventions assigned to this group

160 mg PI-88/Day

PI-88 160 mg/day SC injection

Group Type: EXPERIMENTAL

PI-88

Intervention Type: DRUG

Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks

250 mg PI-88/Day

PI-88 250 mg/day SC injection

Group Type: EXPERIMENTAL

PI-88

Intervention Type: DRUG

Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks

Interventions

PI-88

Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medigen Biotechnology Corporation

INDUSTRY

Sponsor Role: collaborator

Cellxpert Biotechnology Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pei-Jer Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital-Linkou Medical Centre

Taoyuan District, , Taiwan

Countries

Taiwan

References

Liu CJ, Chang J, Lee PH, Lin DY, Wu CC, Jeng LB, Lin YJ, Mok KT, Lee WC, Yeh HZ, Ho MC, Yang SS, Yang MD, Yu MC, Hu RH, Peng CY, Lai KL, Chang SS, Chen PJ. Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence. World J Gastroenterol. 2014 Aug 28;20(32):11384-93. doi: 10.3748/wjg.v20.i32.11384.

Reference Type: DERIVED

PMID: 25170226 (View on PubMed)

Liu CJ, Lee PH, Lin DY, Wu CC, Jeng LB, Lin PW, Mok KT, Lee WC, Yeh HZ, Ho MC, Yang SS, Lee CC, Yu MC, Hu RH, Peng CY, Lai KL, Chang SS, Chen PJ. Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage. J Hepatol. 2009 May;50(5):958-68. doi: 10.1016/j.jhep.2008.12.023. Epub 2009 Feb 15.

Reference Type: DERIVED

PMID: 19303160 (View on PubMed)

Other Identifiers

PR88204

Identifier Type: OTHER

Identifier Source: secondary_id

MG 002

Identifier Type: -

Identifier Source: org_study_id