Clinical trial NCT00247728: PI-88 in Hepatocellular Carcinoma After Hepatectomy
Official title: A Randomized, Multi-centre, Efficacy Evaluation of PI-88 in Patients With Hepatocellular Carcinoma After Hepatectomy - A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: PI-88
post resection hepatoma
adjuvant therapy
hepatectomy
hepatoma
Lead sponsor: Cellxpert Biotechnology Corp.
Sponsor class: INDUSTRY
Collaborators: name: Medigen Biotechnology Corporation
First posted: 2005-11-02
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Tumour Non-recurrence Rate
timeFrame: Week 48
Secondary outcomes:
measure: Time to Recurrence
timeFrame: until confirmed tumour recurrence, or for a maximum of 48 weeks
measure: Survival Rate
timeFrame: Week 48
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital-Linkou Medical Centre
Study officials:
affiliation: National Taiwan University Hospital
name: Pei-Jer Chen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.