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

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ClinicalTrials.gov Identifier: NCT01402908
Recruitment Status : Terminated (Due to Interim Analysis and business concerns)
First Posted : July 26, 2011
Results First Posted : December 30, 2020
Last Update Posted : December 30, 2020
Sponsor:
Information provided by (Responsible Party):
Medigen Biotechnology Corporation

Tracking Information
First Submitted Date  ICMJE July 25, 2011
First Posted Date  ICMJE July 26, 2011
Results First Submitted Date  ICMJE October 19, 2020
Results First Posted Date  ICMJE December 30, 2020
Last Update Posted Date December 30, 2020
Study Start Date  ICMJE August 2011
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2011)
Disease-Free Survival (DFS) [ Time Frame: 1 year ]
To evaluate the efficacy of daily administration of PI-88 versus placebo for the adjuvant treatment of study subjects as measured by disease free survival (DFS) during the study period.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2020)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2011)
  • Time to Recurrence (TTR) [ Time Frame: 1 year ]
    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 ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer
  • Liver Cancer
  • Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: PI-88
    Lyophilized powder reconstituted to provide 160 mg of PI-88
    Other Name: Muparfostat
  • Other: Placebo
    Lactose lyophilized powder
Study Arms  ICMJE
  • Experimental: PI-88
    Arm 1
    Intervention: Drug: PI-88
  • Placebo Comparator: Placebo
    Arm 2
    Intervention: Other: Placebo
Publications * 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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 12, 2014)
520
Original Actual Enrollment  ICMJE
 (submitted: July 25, 2011)
500
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China,   Hong Kong,   Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01402908
Other Study ID Numbers  ICMJE CT-PI-31
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Medigen Biotechnology Corporation
Study Sponsor  ICMJE Medigen Biotechnology Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pei-Jer Chen, MD National Taiwan University Hospital
PRS Account Medigen Biotechnology Corporation
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP