A Phase III Study of PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related Hepatocellular Carcinoma After Surgical Resection (PATRON)

• Time to Recurrence (TTR) [ Time Frame: End of study ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.
• Overall Survival (OS) [ Time Frame: End of study ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.
• Tumor Recurrence (TR) rate [ Time Frame: End of study ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.

• Time to recurrence (TTR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.
• overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.
• Tumor recurrence (TR) rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  The secondary objectives are to evaluate (a) safety and (b) efficacy, as measured by time to recurrence (TTR), overall survival (OS), tumor recurrence (TR) rate.

The purpose of this study is to determine if PI-88 is effective and safe in patients who have had surgery to remove primary liver cancer.

Primary liver cancer (hepatocellular carcinoma or HCC) is the fifth most common cancer worldwide. Surgery to remove the tumour remains the principal form of treatment for liver cancer, however recurrence of the disease after surgery is common and survival after recurrence is poor. At the moment there is no recommended standard treatment for HCC immediately after the tumour has been removed surgically. PI-88 is a new experimental drug which blocks the growth of new blood vessels in tumours to stop the tumour growing (starves it of food) and also stops tumour cells spreading. Previous experience with PI-88 has shown it has been well tolerated and has shown some benefit in delaying the time it takes for the hepatocellular carcinoma to reappear after surgery. The purpose of this study is to determine if PI-88 is effective and safe in patients who have had surgery to remove primary liver cancer.

• Cancer
• Liver Cancer
• Hepatocellular Carcinoma

• Drug: PI-88
  Lyophilized powder reconstituted to provide 160 mg of PI-88
• Other: Placebo
  Lactose lyophilized powder

• Experimental: PI-88
  Arm 1
  Intervention: Drug: PI-88
• Placebo Comparator: Placebo
  Arm 2
  Intervention: Other: Placebo

The key inclusion criteria are listed below:

• Histological diagnosis of primary HCC
• Curative resection within 4-6 weeks prior to randomisation (proven by clear resection margin (> 0.1 cm) + negative chest and tri-phasic contrast enhanced spiral CT scan + negative abdominal contrast enhanced MRI). Patients with residual lymph node metastases should not be enrolled.
• Known positive serum HBsAg or known HCV in serum
• ECOG PS 0-1
• Child Pugh score < 8

The key exclusion criteria are listed below:

• Pathological confirmation of single tumour <2cm in diameter from most recent hepatectomy
• History of immune-mediated thrombocytopenia, other platelet disorders, laboratory evidence of anti-heparin antibodies, or prior history thereof
• Metastatic tumour or co-existing malignant disease
• Prior history of malignancy except non-melanomatous skin cancer or treated in-situ carcinoma of the cervix
• Prior recurrence of HCC or any liver resection prior to the most recent resection
• Prior HCC therapy including chemotherapy, radiotherapy, molecular targeted agents, vaccines, liver transplantation or surgical resection prior to most recent hepatectomy. Pre-operative portal vein embolisation is permitted
• Planned liver transplantation
• History of allergic and/or hypersensitivity and/or significant adverse reactions to heparin or other anticoagulants
• Concomitant aspirin (>150mg/day), vitamin K antagonists (other than low dose prophylaxis), NSAIDs (except COX-2 inhibitors), heparin within 2 weeks prior to randomisation or other anti-platelet drugs.
• History of allergic, anaphylactic or significant adverse reaction to radiographic contrast media which cannot be managed by pre-treatment prophylaxis or patient unsuitable for CT or MRI scanning.
• Known seropositivity to HIV
• Inflammatory bowel disease , abnormal bleeding tendency or at risk of bleeding due to open wounds or planned surgery
• Acute substance abuse including alcohol
• Anticancer therapy or investigational agent in the previous 4 weeks