Phase I Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma

A Phase I Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Biological: OBP-301

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 Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Recruiting
    • Pusan National University Hospital
• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Pei-Jer Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged 18 to 65 years (19 to 65 years in Korea), either sex
2. Patients diagnosed with hepatocellular carcinoma. The diagnosis of HCC (hepatocellular carcinoma) should be established by cytology or histopathology

3. Patients who have unresectable HCC and meet all of the following conditions:

   • Barcelona Clinic Liver Cancer (BCLC) stage B or C
   • TransAarterial ChemoEmbolization (TACE) refractory in discretion of the investigators, or TACE unsuitable (such as but not limited to portal vein thrombosis)
   • Local ablative treatment (such as percutaneous ethanol injection, radiofrequency ablation, etc) unsuitable
   • Sorafenib failure, intolerable or ineligible
4. 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
5. Patients who have Child-Pugh's Score no greater than 7, and have no ascites

6. Patients who have all the conditions below at screening:

   serum ALT (Alanine Aminotransferase) level (GPT) less than 2.5 x UNL

   • serum AST (Aspartate Aminotransferase) level (GOT) less than 2.5 x UNL
   • WBC (white blood cell) greater than or equal to 3,000 / microliter
   • Serum creatinine less than or equal to 1.5 x UNL
   • activated partial thromboplastin time (APTT) <1.5 x UNL
7. Platelet count correctable to greater than or equal to 80,000 / microliter
8. prothrombin time-international normalized ratio (PT-INR) correctable to less than 1.5
9. Patients who have life expectancy longer than 12 weeks

Exclusion Criteria:

1. Patients who have had chemotherapy within last three weeks (6 weeks for nitrosourea or Mitomycin-C) prior to dosing
2. 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
3. Patients who have received other investigational or antineoplastic medication within the last four weeks prior to dosing
4. Patients who had history of esophageal variceal bleeding within eight weeks prior to study entry
5. 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
6. Patients who had acute viral infection syndrome diagnosed within the last two weeks
7. Patients who have concomitant hematological malignancy (e.g. acute lymphocytic leukemia, non-Hodgkin's lymphoma)
8. Patients who have active rheumatoid arthritis or other autoimmune disease.
9. 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)
10. Patients with organ transplants (may require prolonged immunosuppressive therapy)
11. Patients who had prior participation in any research protocol which involved administration of adenovirus vectors
12. Patients received any immune-related related related related related blood products, such as immunoglobulin in the prior 3 months
13. 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
14. Psychiatric, addictive, or any disorder which compromises ability to give truly informed consent for participation in this study or adequate compliance
15. Female patients that are pregnant or on breast-feeding
16. Patients who receive anti-platelet agents or anti-coagulation agents (e.g. Heparin, warfarin, aspirin, ticlopidine, clopidogrel, dipyridamole and so on).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of safety parameters (adverse events, laboratory data, EKG, body weight, vital signs) on patient-base.	14 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Oncolys BioPharma Inc
• Collaborators: Medigen Biotechnology Corporation
• Investigators: Study Chair: Pei-Jer Chen, M.D., Ph.D., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 18, 2014

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CT-OT-21