Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma
This study is an open-label, multi-center, phase 1, dose escalation study with a phase 2 expansion cohort to determine the safety, pharmacokinetics and preliminary anti-tumor activity of intravenous TKM-080301 in subjects with advanced hepatocellular carcinoma (HCC).
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
Liver Cancer, Adult
Liver Cell Carcinoma, Adult
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-Label, Multi-Center, Phase 1, Dose Escalation Study With Phase 2 Expansion Cohort to Determine the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma|
- Maximum tolerated dose (MTD) [ Time Frame: Up to 6 months after initial dose. ]Laboratory assessments
- Preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Upon every 2 cycles of treatment for up to 6 months ]Obtain preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
- Clinical Benefit Rate at maximum tolerated dose (MTD) in Expansion Cohort [ Time Frame: Upon completion of treatment of expansion cohort; up to 6 months after last participant is dosed. ]Assessed after completion of Phase 2.
- Assessment of Pharmacodynamic Effect [ Time Frame: Upon completion of cycle 1 and cycle 2 treatment; 1 and 2 months after last participant is dosed in expansion cohort. ]Assessment of target mRNA reduction in participants consenting to pre- and post-treatment tumor biopsies.
|Study Start Date:||June 2014|
|Study Completion Date:||July 2016|
|Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: 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 intravenous infusion
Other Name: PLK1-HCC
Study design: Open label, multi-center, 3 + 3 dose-escalation study with an expansion cohort at the maximum tolerated dose (MTD) to investigate safety, tolerability, PK, and preliminary anti-tumor activity of TKM 080301 in subjects with HCC.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02191878
|United States, Arizona|
|Arizona Clinical Research Center|
|Tucson, Arizona, United States, 85715|
|United States, California|
|University of California San Francisco|
|San Francisco, California, United States, 94115|
|United States, Missouri|
|Kansas City Research Institute|
|Kansas City, Missouri, United States, 64131|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New york, New York, United States, 10065|
|United States, Texas|
|Mary Crowley Cancer Research Centers|
|Dallas, Texas, United States, 75230|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada|
|Queen Mary Hospital|
|Hong Kong, China|
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Gyeonggi-do, Korea, Republic of, 110744|
|Samsung Medical Center|
|Seoul, Gyeonggi-do, Korea, Republic of, 135-710|
|ASAN Medical Center|
|Seoul, Gyeonggi-do, Korea, Republic of, 138-736|
|Severence Hospital, Yonsei, University Health System|
|Seoul, Korea, Republic of|
|National University Hospital|
|National Taiwan University Hospital|
|Taipei Medical University Hospital, Shuang-Ho Hospital|
|Taipei Veterans General Hospital|
|Study Director:||Mark Kowalski, M.D., Ph.D.||Tekmira Pharmaceuticals|