Carcinoma, Hepatocellular
Conditions
Keywords
PI-88, post resection hepatoma, adjuvant therapy, hepatectomy, hepatoma
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.
Interventions
DRUGPI-88
Once-daily SC injection for four consecutive days per week, for 3 weeks out of every 4 weeks
Sponsors
Medigen Biotechnology Corporation
Cellxpert Biotechnology Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumour Non-recurrence Rate | Week 48 | The tumor non-recurrence rate at the end of the 48-week study period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence | until confirmed tumour recurrence, or for a maximum of 48 weeks | Time to recurrence during the 48-week study period |
| Survival Rate | Week 48 | Survival rate at the end of the 48-week study period |
Countries
Taiwan
Participant flow
Recruitment details
215 patients were screened between June 2004 and December 2006. Patients were randomized in balanced blocks per center.
Participants by arm
| Arm | Count |
|---|---|
| Group A - Untreated Control untreated control with standard of care, ITT population | 58 |
| Group B - 160 mg PI-88/Day 160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, ITT population | 56 |
| Group C - 250 mg PI-88/Day 250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, ITT population | 54 |
| Total | 168 |
Baseline characteristics
| Characteristic | Group A - Untreated Control | Group B - 160 mg PI-88/Day | Group C - 250 mg PI-88/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 54.96 years STANDARD_DEVIATION 12.54 | 51.47 years STANDARD_DEVIATION 12.57 | 52.41 years STANDARD_DEVIATION 12.03 | 52.39 years STANDARD_DEVIATION 12.38 |
| Region of Enrollment Taiwan | 58 participants | 56 participants | 54 participants | 168 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 10 Participants | 35 Participants |
| Sex: Female, Male Male | 43 Participants | 46 Participants | 44 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 58 | 55 / 57 | 54 / 57 |
| serious Total, serious adverse events | 1 / 58 | 7 / 57 | 8 / 57 |
Outcome results
Primary
Tumour Non-recurrence Rate
The tumor non-recurrence rate at the end of the 48-week study period
Time frame: Week 48
Population: ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A - Untreated Control | Tumour Non-recurrence Rate | 32 Participants |
| Group B - 160 mg PI-88/Day | Tumour Non-recurrence Rate | 40 Participants |
| Group C - 250 mg PI-88/Day | Tumour Non-recurrence Rate | 35 Participants |
p-value: 0.072Chi-squared
p-value: 0.298Chi-squared
Secondary
Survival Rate
Survival rate at the end of the 48-week study period
Time frame: Week 48
Population: ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A - Untreated Control | Survival Rate | 54 Participants |
| Group B - 160 mg PI-88/Day | Survival Rate | 51 Participants |
| Group C - 250 mg PI-88/Day | Survival Rate | 51 Participants |
Secondary
Time to Recurrence
Time to recurrence during the 48-week study period
Time frame: until confirmed tumour recurrence, or for a maximum of 48 weeks
Population: ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A - Untreated Control | Time to Recurrence | NA Weeks |
| Group B - 160 mg PI-88/Day | Time to Recurrence | NA Weeks |
| Group C - 250 mg PI-88/Day | Time to Recurrence | NA Weeks |
p-value: 0.087Mantel Haenszel
p-value: 0.653Mantel Haenszel