Clinical trial NCT01402908: A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection
Official title: A Prospective, Randomized, Double-blind, Placebo Controlled, Parallel-group, International Multicenter Phase III Trial of PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cancer
Liver Cancer
Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
PI-88
Phase III
Adjuvant Therapy
Hepatoma
Liver Cancer
Lead sponsor: Cellxpert Biotechnology Corp.
Sponsor class: INDUSTRY
Collaborators: name: Medigen Biotechnology Corporation
First posted: 2011-07-26
Enrollment: 520
Sex: ALL
Minimum age (years): 18
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 determine if PI-88 is effective and safe in patients who have had surgery to remove primary liver cancer.

Detailed description: 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.

Eligibility criteria: Key inclusion criteria:

1. Histologically-proven primary hepatocellular carcinoma with curative resection performed in the 4 - 6 weeks prior to randomization.
2. Age ≥ 18 years.
3. Written, signed and dated informed consent to participate in study
4. ECOG performance status 0 to 1
5. Child Pugh score ≤ 8
6. Platelet count ≥ 80 x 109 cells/liter
7. PT-INR ≤ 1.3
8. aPTT ≤ upper limit of normal

Key exclusion criteria:

1. Pathological confirmation of single tumor \< 2 cm in diameter which obtained from the most recent hepatectomy.
2. History of immune-mediated thrombocytopenia other platelet abnormalities or other hereditary or acquired coagulopathies, or laboratory evidence of anti-heparin antibodies, or any previous history of having tested positive for anti-heparin antibodies.
3. Any evidence of tumor metastasis or co-existing malignant disease
4. Any prior recurrence of HCC or any liver resection prior to the most recent procedure
5. Clinically significant non-malignant disease including, but not limited to, surgery within 6 weeks of randomization (apart from liver resection and re-operation for complications of liver resection), active clinically significant infection within 6 weeks prior to randomization, myocardial infarction within 6 months prior to randomization, cerebrovascular event within 12 months prior to randomization or clinically-significant gastrointestinal bleeding within 12 months prior to randomization. Subjects who have experienced post-operative complications of liver resection may be enrolled providing that such complications are fully resolved at the time of screening.
6. Subjects with uncontrolled infection or serious infection within the past 4 weeks.
7. History of prior HCC therapy including chemotherapy, radiotherapy, molecular targeting agents, vaccines, transarterial embolization (TAE), transarterial chemoembolization (TACE), liver transplantation or surgical resection prior to the most recent hepatectomy, at any time prior to randomization. This includes pre-, peri- and post-operative treatments. Pre-operative portal vein embolization is permitted. Subjects should not be enrolled if, at the time of randomization, it is planned that they will subsequently undergo liver transplantation regardless of tumor recurrence.
8. Concomitant use of aspirin (\> 150 mg/day), vitamin K antagonists (other than low-dose prophylactic use), heparin within two weeks prior to randomization, or other anti-platelet drugs (e.g. abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low dose aspirin (≤ 150 mg/day) and low-dose prophylactic vitamin K antagonists (e.g. warfarin ≤ 1 mg/day) are permitted as concomitant medications.
9. History of allergic, anaphylactic or other significant adverse reaction to radiographic contrast media (iodinated or non-iodinated), which cannot be managed by pre-treatment with agents such as steroids or anti-histamines, and which, in the opinion of the investigator, renders the subject unsuitable for routine CT scanning. Subjects who are contra-indicated for CT scanning for other reasons (e.g. ferromagnetic implants, profound claustrophobia), should not be enrolled.
10. Subjects with history of inflammatory bowel disease, any other abnormal bleeding tendency, or subjects at risk of bleeding due to open wounds or planned surgery.
11. Women who are pregnant or breast-feeding or women of child-bearing potential who are unable or unwilling to practice a highly effective means of contraception.
12. Active substance abuse, including alcohol, which, in the opinion of the investigator, risks impairing the ability of the subject to comply with the protocol.
13. Subjects who received other investigational or anti-neoplastic medication within the past 4 weeks.
14. Current participation in any other clinical study or research project which involves administration of a pharmaceutical product or experimental treatment, or which involves protocol-specified laboratory tests, imaging studies or other investigations.

Primary outcomes:
measure: Disease-Free Survival (DFS)
timeFrame: End of study
Secondary outcomes:
measure: Time to Recurrence (TTR)
timeFrame: Time to recurrence (TTR) was defined as the time from randomization to the first time that tumor recurrence was observed or suspected during the study period (3 years).
measure: Overall Survival (OS)
timeFrame: Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period (3 years).
measure: Tumor Recurrence Rate (TR Rate)
timeFrame: The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: The General Hospital of People's Liberation Army (301 hospital)
city: Shanghai
country: China
facility: Fudan University Zhongshan Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Pusan
country: Korea, Republic of
facility: Kyungpook National University Hospital (KNUH)
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital (PNUH)
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital (PNUYH)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: E-Da Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial 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 City
country: Taiwan
facility: Taipei Veterans General 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
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gnoni A, Santini D, Scartozzi M, Russo A, Licchetta A, Palmieri V, Lupo L, Faloppi L, Palasciano G, Memeo V, Angarano G, Brunetti O, Guarini A, Pisconti S, Lorusso V, Silvestris N. Hepatocellular carcinoma treatment over sorafenib: epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel? Expert Opin Ther Targets. 2015;19(12):1623-35. doi: 10.1517/14728222.2015.1071354. Epub 2015 Jul 27.