A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection

NCT01402908 | Terminated Phase 3 Results DMC

• 1 other identifier: CT-PI-31
• Study Type: interventional
• Target: 520
• Locations: 4 countries
• Sites: 25

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.

Conditions

Cancer; Liver Cancer; Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; PI-88; Phase III; Adjuvant Therapy; Hepatoma; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival (DFS)

  To evaluate the efficacy of daily administration of PI-88 versus placebo for the adjuvant treatment of study subjects as measured by DFS during study period. As the median DFS could not be estimated, the overall 25 th percentile DFS was reported.

  End of study

Secondary Outcomes (3)

• Time to Recurrence (TTR)

  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).

• Overall Survival (OS)

  Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period (3 years).

• Tumor Recurrence Rate (TR Rate)

  The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.

Study Arms (2)

PI-88

EXPERIMENTAL

Arm 1

Drug: PI-88

Placebo

PLACEBO COMPARATOR

Arm 2

Other: Placebo

Interventions

PI-88 DRUG

Lyophilized powder reconstituted to provide 160 mg of PI-88

Also known as: Muparfostat

PI-88

Placebo OTHER

Lactose lyophilized powder

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pathological confirmation of single tumor \< 2 cm in diameter which obtained from the most recent hepatectomy.
• 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.
• Any evidence of tumor metastasis or co-existing malignant disease
• Any prior recurrence of HCC or any liver resection prior to the most recent procedure
• 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.
• Subjects with uncontrolled infection or serious infection within the past 4 weeks.
• 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.
• 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.
• 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.
• 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.
• 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.
• Active substance abuse, including alcohol, which, in the opinion of the investigator, risks impairing the ability of the subject to comply with the protocol.
• Subjects who received other investigational or anti-neoplastic medication within the past 4 weeks.
• 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.

Sponsors & Collaborators

• Cellxpert Biotechnology Corp.: lead
• Medigen Biotechnology Corporation: collaborator

Study Sites (25)

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

The General Hospital of People's Liberation Army (301 hospital)

Beijing, China

Location

Fudan University Zhongshan Hospital

Shanghai, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Kyungpook National University Hospital (KNUH)

Pusan, South Korea

Location

Pusan National University Hospital (PNUH)

Pusan, South Korea

Location

Pusan National University Yangsan Hospital (PNUYH)

Pusan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul St. Mary Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

E-Da Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital-Linkou Medical Centre

Taoyuan District, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 26212068 DERIVED

MeSH Terms

Conditions

Neoplasms; Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

phosphomannopentaose sulfate

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Clinical Research Manager
• Organization: Medigen Biotechnology Corp.

Doyce.Chen@medigen.com.tw

886-2-77361234

Study Officials

• Pei-Jer Chen, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 26, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: January 1, 2015
• Last Updated: June 23, 2022
• Results First Posted: December 30, 2020

Record last verified: 2022-06

Locations

KR (11); TW (9); HK (1); CN (4)