PI-88 in Hepatocellular Carcinoma After Hepatectomy

• ClinicalTrials.gov Identifier: NCT00247728
• Recruitment Status: Completed
• First Posted: November 2, 2005
• Results First Posted: November 12, 2020
• Last Update Posted: November 12, 2020
• Sponsor: Medigen Biotechnology Corporation
• Collaborator: Progen Pharmaceuticals
• Information provided by (Responsible Party): Medigen Biotechnology Corporation

Tracking Information

• First Submitted Date: November 1, 2005
• First Posted Date: November 2, 2005
• Results First Submitted Date: July 27, 2011
• Results First Posted Date: November 12, 2020
• Last Update Posted Date: November 12, 2020
• Study Start Date: June 2004
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2020)

Tumour Non-recurrence Rate [ Time Frame: Week 48 ]

The tumor non-recurrence rate at the end of the 48-week study period

• Original Primary Outcome Measures (submitted: November 1, 2005): Tumour Non-recurrence Rate

Current Secondary Outcome Measures (submitted: October 19, 2020)

• Time to Recurrence [ Time Frame: until confirmed tumour recurrence, or for a maximum of 48 weeks ]
  Time to recurrence during the 48-week study period
• Survival Rate [ Time Frame: Week 48 ]
  Survival rate at the end of the 48-week study period

Original Secondary Outcome Measures (submitted: November 1, 2005)

• Time to first recurrence
• Survival Rate

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Hepatocellular

Intervention

Drug: PI-88

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

Study Arms

• No Intervention: Untreated Control
  Untreated control arm
• Experimental: 160 mg PI-88/Day
  PI-88 160 mg/day SC injection
  Intervention: Drug: PI-88
• Experimental: 250 mg PI-88/Day
  PI-88 250 mg/day SC injection
  Intervention: Drug: PI-88

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 19, 2020): 172
• Original Enrollment (submitted: November 1, 2005): 343
• Actual Study Completion Date: June 2008
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT00247728
• Other Study ID Numbers: MG 002; PR88204 ( Other Identifier: Alternate protocol identifier set by company )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Medigen Biotechnology Corporation
• Study Sponsor: Medigen Biotechnology Corporation
• Collaborators: Progen Pharmaceuticals

Investigators

• Principal Investigator: Pei-Jer Chen, MD, PhD; National Taiwan University Hospital

• PRS Account: Medigen Biotechnology Corporation
• Verification Date: October 2020