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

June 21, 2022 updated by: Cellxpert Biotechnology Corp.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

520

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Peking Union Medical College Hospital
      • Beijing, China
        • The General Hospital of People's Liberation Army (301 Hospital)
      • Shanghai, China
        • Fudan University Zhongshan Hospital
    • Hunan
      • Changsha, Hunan, China
        • The Third Xiangya Hospital of Central South University
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
  • Korea, Republic of
      • Pusan, Korea, Republic of
        • Kyungpook National University Hospital (KNUH)
      • Pusan, Korea, Republic of
        • Pusan National University Hospital (PNUH)
      • Pusan, Korea, Republic of
        • Pusan National University Yangsan Hospital (PNUYH)
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Gangnam Severance Hospital
      • Seoul, Korea, Republic of
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of
        • Seoul St. Mary Hospital
      • Suwon, Korea, Republic of
        • Ajou University Hospital
  • Taiwan
      • Changhua City, Taiwan
        • Changhua Christian Hospital
      • Kaohsiung, Taiwan
        • Chang Gung Memorial Hospital
      • Kaohsiung City, Taiwan
        • E-DA hospital
      • Taichung, Taiwan
        • China Medical University Hospital
      • Taichung, Taiwan
        • Taichung Veterans General Hospital
      • Tainan, Taiwan
        • National Cheng Kung University Hospital
      • Taipei, Taiwan
        • National Taiwan University Hospital
      • Taipei City, Taiwan
        • Taipei Veterans General Hospital
      • Taoyuan, Taiwan
        • Chang Gung Memorial Hospital-Linkou Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PI-88
Arm 1
Drug: PI-88
Lyophilized powder reconstituted to provide 160 mg of PI-88
Other Names:
  • Muparfostat
Placebo Comparator: Placebo
Arm 2
Other: Placebo
Lactose lyophilized powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-Free Survival (DFS)
Time Frame: End of study

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Recurrence (TTR)
Time Frame: 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).

As no subjects died without a preceding tumor recurrence , no median time to TTR could be estimated in the present study. And therefore the overall 25th percentile DFS was reported.

The results of time to recurrence (TTR) were the same as that of DFS, as no subjects died without a preceding tumor recurrence.
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)
Time Frame: Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period (3 years).
Overall survival was defined as the time, in weeks, from randomization to death from any cause during the study period.
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)
Time Frame: The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.
TR rate was to calculate number of subjects with recurrence among the analyzed population.
The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cellxpert Biotechnology Corp.

Collaborators

Medigen Biotechnology Corporation

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

July 25, 2011

First Submitted That Met QC Criteria

July 25, 2011

First Posted (Estimate)

July 26, 2011

Study Record Updates

Last Update Posted (Actual)

June 23, 2022

Last Update Submitted That Met QC Criteria

June 21, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-PI-31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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