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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Medigen Biotechnology Corporation
ClinicalTrials.gov Identifier:
NCT01402908
First received: July 25, 2011
Last updated: October 12, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Liver Cancer
Hepatocellular Carcinoma
Drug: PI-88
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Hepatocellular Carcinoma After Surgical Resection

Resource links provided by NLM:


Further study details as provided by Medigen Biotechnology Corporation:

Primary Outcome Measures:
  • Disease-Free Survival (DFS) [ Time Frame: End of study ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Time to Recurrence (TTR) [ Time Frame: End of study ] [ Designated as safety issue: No ]
    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: End of study ] [ Designated as safety issue: No ]
    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: End of study ] [ Designated as safety issue: No ]
    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.


Enrollment: 520
Study Start Date: August 2011
Estimated Study Completion Date: December 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PI-88
Arm 1
Drug: PI-88
Lyophilized powder reconstituted to provide 160 mg of PI-88
Other Name: Muparfostat
Placebo Comparator: Placebo
Arm 2
Other: Placebo
Lactose lyophilized powder

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402908

Locations
China, Hunan
The Third Xiangya Hospital of Central South University
Changsha, Hunan, China
China
The General Hospital of People's Liberation Army (301 hospital)
Beijing, China
Peking Union Medical College Hospital
Beijing, China
Fudan University Zhongshan Hospital
Shanghai, China
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Korea, Republic of
Pusan National University Hospital (PNUH)
Pusan, Korea, Republic of
Kyungpook National University Hospital (KNUH)
Pusan, Korea, Republic of
Pusan National University Yangsan Hospital (PNUYH)
Pusan, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul St. Mary Hospital
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Gangnam Severance Hospital
Seoul, Korea, Republic of
Korea University Guro Hospital
Seoul, Korea, Republic of
Ajou University Hospital
Suwon, Korea, Republic of
Taiwan
Changhua Christian Hospital
Changhua City, Taiwan
Chang Gung Memorial Hospital
Kaohsiung, Taiwan
E-Da Hospital
Kaohsiung City, Taiwan
Chang Gung Memorial Hospital-Linkou Medical Centre
Kwei-Shan, Taiwan
China Medical University Hospital
Taichung, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei City, Taiwan
Sponsors and Collaborators
Medigen Biotechnology Corporation
Investigators
Principal Investigator: Pei-Jer Chen, MD National Taiwan University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Medigen Biotechnology Corporation
ClinicalTrials.gov Identifier: NCT01402908     History of Changes
Other Study ID Numbers: CT-PI-31
Study First Received: July 25, 2011
Last Updated: October 12, 2014
Health Authority: United States: Food and Drug Administration
Taiwan: Ministry of Health and Welfare
South Korea: Korea Food and Drug Administration (KFDA)
China: Food and Drug Administration
Hong Kong: Department of Health

Keywords provided by Medigen Biotechnology Corporation:
Hepatocellular Carcinoma
PI-88
Phase III
Adjuvant Therapy
Hepatoma
Liver Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 20, 2014