Phase I Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma
Study Details
Study Description
Brief Summary
This is an open labeled, multiple centers, two countries (Taiwan and Korea) non-comparative phase I trial in patients with hepatocellular carcinoma. In phase I part, a maximum of 18 patients will be recruited in this study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
After screening, each eligible patient will undergo a treatment of OBP-301 within 14 days and will automatically enter follow-up period.
The follow-up period is up to 12 weeks after the last injection in the phase I part.
Each patient will return for follow-up visit weekly in the first month after the last injection, and then every 4 weeks up to the end of follow-up period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: single intra-tumoral injection OBP-301 ; Cohort 1: 1x10 10 viral particle (VP)/ tumor Cohort 2: 1x10 11 viral particle (VP)/ tumor Cohort 3: 1x10 12 viral particle (VP)/ tumor |
Biological: OBP-301
A range of dose levels is investigated and the starting dose is 1x1010 VP/tumor. Dose administration will be conducted through a dose-escalating scheme from 1x1010 VP/tumor to 1x1011 VP/tumor, 1x1012 VP/tumor, 3x1011 VP/tumor and 3x1012 VP/tumor.
|
Outcome Measures
Primary Outcome Measures
- Evaluation of safety parameters (adverse events, laboratory data, EKG, body weight, vital signs) on patient-base. [14 weeks]
Secondary Outcome Measures
- Maximum Tolerated Dose (MTD)/ Maximum Feasible Dose (MFD) for patients using OBP-301. [16 weeks]
- Dose-Limiting Toxicity (DLT) for patients using OBP-301. [28 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients aged 18 to 65 years (19 to 65 years in Korea), either sex
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Patients diagnosed with hepatocellular carcinoma. The diagnosis of HCC (hepatocellular carcinoma) should be established by cytology or histopathology
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Patients who have unresectable HCC and meet all of the following conditions:
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Barcelona Clinic Liver Cancer (BCLC) stage B or C
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TransAarterial ChemoEmbolization (TACE) refractory in discretion of the investigators, or TACE unsuitable (such as but not limited to portal vein thrombosis)
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Local ablative treatment (such as percutaneous ethanol injection, radiofrequency ablation, etc) unsuitable
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Sorafenib failure, intolerable or ineligible
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Patients must have at least one lesion that can be accurately measured in at least one dimension as 1 cm or more and the lesion must be suitable for repeat measurement
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Patients who have Child-Pugh's Score no greater than 7, and have no ascites
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Patients who have all the conditions below at screening:
serum ALT (Alanine Aminotransferase) level (GPT) less than 2.5 x UNL
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serum AST (Aspartate Aminotransferase) level (GOT) less than 2.5 x UNL
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WBC (white blood cell) greater than or equal to 3,000 / microliter
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Serum creatinine less than or equal to 1.5 x UNL
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activated partial thromboplastin time (APTT) <1.5 x UNL
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Platelet count correctable to greater than or equal to 80,000 / microliter
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prothrombin time-international normalized ratio (PT-INR) correctable to less than 1.5
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Patients who have life expectancy longer than 12 weeks
Exclusion Criteria:
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Patients who have had chemotherapy within last three weeks (6 weeks for nitrosourea or Mitomycin-C) prior to dosing
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Patients who have had radiotherapy to tumor site within the last four weeks prior to dosing and with documentation of subsequent tumor growth at this site
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Patients who have received other investigational or antineoplastic medication within the last four weeks prior to dosing
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Patients who had history of esophageal variceal bleeding within eight weeks prior to study entry
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Patients who have uncontrolled diabetes, active or chronic infection, including HIV, except for asymptomatic bacterial colonization, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
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Patients who had acute viral infection syndrome diagnosed within the last two weeks
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Patients who have concomitant hematological malignancy (e.g. acute lymphocytic leukemia, non-Hodgkin's lymphoma)
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Patients who have active rheumatoid arthritis or other autoimmune disease.
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Patients who have current requirement for chronic systemic immunosuppressive medication including any dose of glucocorticoid or cyclosporin, or chronic use of any such medication within the last four weeks Note: Course of glucocorticoid therapy less than 10 days duration is allowed (e.g. for nausea control)
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Patients with organ transplants (may require prolonged immunosuppressive therapy)
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Patients who had prior participation in any research protocol which involved administration of adenovirus vectors
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Patients received any immune-related related related related related blood products, such as immunoglobulin in the prior 3 months
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Patients who have uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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Psychiatric, addictive, or any disorder which compromises ability to give truly informed consent for participation in this study or adequate compliance
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Female patients that are pregnant or on breast-feeding
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Patients who receive anti-platelet agents or anti-coagulation agents (e.g. Heparin, warfarin, aspirin, ticlopidine, clopidogrel, dipyridamole and so on).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pusan National University Hospital | Busan | Korea, Republic of | 602-739 | |
| 2 | National Taiwan University Hospital | Taipei | Taiwan | 10002 |
Sponsors and Collaborators
- Oncolys BioPharma Inc
- Medigen Biotechnology Corporation
Investigators
- Study Chair: Pei-Jer Chen, M.D., Ph.D., National Taiwan University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT-OT-21