Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma
NCT ID: NCT02191878
Last Updated: 2019-01-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
43 participants
INTERVENTIONAL
2014-06-30
2016-07-31
Brief Summary
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This study is being done to:
* Test the safety and tolerability of TKM-080301 in subjects with advanced hepatocellular carcinoma
* Find the highest dose of TKM-080301 that can be given without causing side effects, called the maximum tolerated dose (MTD).
* Provide a preliminary assessment of anti-tumor activity of TKM-080301
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Detailed Description
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Sequential cohorts of 3 to 6 subjects will receive escalating doses of TKM 080301 according to a pre-specified dose escalation scheme. Assessment of dose-limiting toxicities (DLTs) will be made during Cycle 1 to determine the maximum tolerated dose (MTD). Once the MTD level is established, approximately 20 subjects will be enrolled in an expansion cohort to further confirm the safety and tolerability of TKM-080301 at the MTD.
Study Population: A minimum of 9 and up to approximately 18 adult male or female subjects with histologically or cytologically confirmed metastatic or locally advanced inoperable HCC and a life expectancy of 3 months or more are planned in the dose escalation phase. Approximately 20 subjects are planned in the expansion cohort.
Study Treatment: TKM-080301 will be administered by intravenous (IV) infusion, once weekly for 3 consecutive weeks followed by a 1 week rest period. This 28-day treatment period constitutes 1 cycle.
Subjects who demonstrate clinical benefit without progression per RECIST 1.1 guidelines may receive treatment beyond 6 cycles if the Investigator considers it is in the best interest of the subject, and only with the approval of the Medical Monitor. Subjects would then continue TKM 080301 therapy until withdrawal of consent, disease progression or unacceptable toxicity occurs.
Pharmacokinetics (PK) Subjects will undergo blood sample collection for PK analysis during cycles 1 and 2.
Study Duration: Each treatment cycle will have duration of 28 days and each subject will typically receive up to 6 cycles of treatment. The total duration of the study is expected to be approximately 28 months.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Phase 1 Escalation / Phase 2 Expansion
Phase 1 - dose escalation with intravenous infusion of TKM-080301 to determine MTD.
Phase 2 - dose expansion at the MTD.
TKM-080301
TKM-080301 intravenous infusion
Interventions
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TKM-080301
TKM-080301 intravenous infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5.0 × ULN
* Total bilirubin ≤3.0 mg/dL
* Platelets ≥75,000 /mL
* International Normalized Ratio (INR) ≤1.7
* Subjects must meet the protocol-defined criteria for both hepatitis B virus (HBV) and hepatitis C virus (HCV) status
Exclusion Criteria
* History of liver transplant.
* Diagnosis of fibrolamellar HCC or tumors of mixed histology.
* Subjects known to be positive for Human immunodeficiency virus (HIV) infection.
* Known central nervous system (CNS) or brain metastases.
* Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.
* Symptomatic encephalopathy within 3 months prior to the first dose of TKM-080301 and/or requirement for medication for encephalopathy.
* Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.
* Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.
* Prior therapy with nitrosoureas or mitomycin within 6 weeks prior to the first dose of TKM-080301.
* Prior therapy with any biologic chemotherapeutic or investigational drug within 5 half-lives or 3 weeks, whichever is longer prior to the first dose of TKM 080301.
18 Years
ALL
No
Sponsors
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Arbutus Biopharma Corporation
INDUSTRY
Responsible Party
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Principal Investigators
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Mark Kowalski, M.D., Ph.D.
Role: STUDY_DIRECTOR
Tekmira Pharmaceuticals
Locations
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Arizona Clinical Research Center
Tucson, Arizona, United States
University of California San Francisco
San Francisco, California, United States
Kansas City Research Institute
Kansas City, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Mary Crowley Cancer Research Centers
Dallas, Texas, United States
Princess Margaret Hospital
Toronto, Ontario, Canada
Queen Mary Hospital
Hong Kong, , China
National University Hospital
Singapore, , Singapore
Seoul National University Hospital
Seoul, Gyeonggi-do, South Korea
Samsung Medical Center
Seoul, Gyeonggi-do, South Korea
ASAN Medical Center
Seoul, Gyeonggi-do, South Korea
Severence Hospital, Yonsei, University Health System
Seoul, , South Korea
National Taiwan University Hospital
Taipei, , Taiwan
Taipei Medical University Hospital, Shuang-Ho Hospital
Taipei, , Taiwan
Taipei Veterans General Hospital
Taipei, , Taiwan
Countries
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References
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El Dika I, Lim HY, Yong WP, Lin CC, Yoon JH, Modiano M, Freilich B, Choi HJ, Chao TY, Kelley RK, Brown J, Knox J, Ryoo BY, Yau T, Abou-Alfa GK. An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma. Oncologist. 2019 Jun;24(6):747-e218. doi: 10.1634/theoncologist.2018-0838. Epub 2018 Dec 31.
Other Identifiers
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TKM-HCC-001
Identifier Type: -
Identifier Source: org_study_id
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