CancerPhase 3PATRONNCT01402908
A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection
A Phase 3 study testing PI-88 in people with Cancer and Liver Cancer, run by Cellxpert Biotechnology Corp. at 25 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Liver Cancer, Hepatocellular Carcinoma
- What is being tested?
- PI-88
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 520 participants
- Where
- 25 sitesin 4 countries
- Study dates
- Aug 2011to Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
South Korea11 sites
Kyungpook National University Hospital (KNUH)
Pusan
Pusan National University Hospital (PNUH)
Pusan
Pusan National University Yangsan Hospital (PNUYH)
Pusan
Asan Medical Center
Seoul
Gangnam Severance Hospital
Seoul
Korea University Guro Hospital
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Seoul St. Mary Hospital
Seoul
Severance Hospital, Yonsei University Health System
Seoul
Ajou University Hospital
Suwon
Taiwan9 sites
Changhua Christian Hospital
Changhua
Chang Gung Memorial Hospital
Kaohsiung City
E-Da Hospital
Kaohsiung City
China Medical University Hospital
Taichung
Taichung Veterans General Hospital
Taichung
National Cheng Kung University Hospital
Tainan
National Taiwan University Hospital
Taipei
Taipei Veterans General Hospital
Taipei
Chang Gung Memorial Hospital-Linkou Medical Centre
Taoyuan
China4 sites
Peking Union Medical College Hospital
Beijing
The General Hospital of People's Liberation Army (301 hospital)
Beijing
The Third Xiangya Hospital of Central South University
Changsha, Hunan
Fudan University Zhongshan Hospital
Shanghai
About this study
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
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.
Read the 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.
- Conditions
- Cancer, Liver Cancer, Hepatocellular Carcinoma
- Being tested
- PI-88, Placebo
- Keywords
- Hepatocellular Carcinoma, PI-88, Phase III, Adjuvant Therapy, Hepatoma, Liver Cancer
- Medical subject headings
- Neoplasms, Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PI-88Drug
Also called Muparfostat
Lyophilized powder reconstituted to provide 160 mg of PI-88
PlaceboOther
Lactose lyophilized powder
| Study group | Role | What they receive |
|---|---|---|
| PI-88 | Experimental | Arm 1 Receives: Drug: PI-88 |
| Placebo | Placebo comparator | Arm 2 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of study
Secondary outcomes (3)
Time to Recurrence (TTR)
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.
Measured: 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.
Measured: 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)
TR rate was to calculate number of subjects with recurrence among the analyzed population.
Measured: The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionJul 2014
- Study completionJan 2015
Why it stopped: Due to Interim Analysis and business concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 520 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cellxpert Biotechnology Corp.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medigen Biotechnology Corporation
- Responsible party
- Sponsor
- Investigators
- Pei-Jer Chen, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402908
- Sponsor's protocol ID
- CT-PI-31
- Acronym
- PATRON
- Status last verified
- Jun 2022
- First submitted
- 25 Jul 2011
- Last updated
- 23 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 26212068
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01402908
- Acronym / sponsor ID
- PATRON / CT-PI-31
- Conditions
- Cancer, Liver Cancer, Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, PI-88, Phase III, Adjuvant Therapy, Hepatoma, Liver Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to Interim Analysis and business concerns
- Enrolment
- 520 participants (actual)
- Lead sponsor
- Cellxpert Biotechnology Corp.Industry (pharma, biotech, devices)
- Collaborators
- Medigen Biotechnology Corporation
- Study start
- Aug 2011
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Posted 30 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PI-88 | Experimental | Drug: PI-88Arm 1 |
| Placebo | Placebo comparator | Other: PlaceboArm 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PI-88Also: MuparfostatLyophilized powder reconstituted to provide 160 mg of PI-88 | Drug | PI-88 |
| PlaceboLactose lyophilized powder | Other | Placebo |
Primary outcome
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.
3 secondary outcomes
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).
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).
Tumor Recurrence Rate (TR Rate)
Time frame: The cumulative tumor recurrence rate at weeks 5, 53, 101 and 149 was reported here.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26212068Gnoni 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pei-Jer Chen, MD principal investigator
National Taiwan University Hospital
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PI-88 in people with Cancer and Liver Cancer, run by Cellxpert Biotechnology Corp. at 25 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in South Korea, Taiwan, China, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-Free Survival (DFS) (time frame: End of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01402908, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2022.