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Trial record 2 of 3 for:    TKM-080301

Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arbutus Biopharma Corporation
ClinicalTrials.gov Identifier:
NCT02191878
First received: July 9, 2014
Last updated: July 20, 2016
Last verified: July 2016
  Purpose

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

Condition Intervention Phase
Hepatocellular Carcinoma
Hepatoma
Liver Cancer, Adult
Liver Cell Carcinoma, Adult
Drug: TKM-080301
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by Arbutus Biopharma Corporation:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: Up to 6 months after initial dose. ] [ Designated as safety issue: Yes ]
    Laboratory assessments


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    Assessed after completion of Phase 2.


Other Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Assessment of target mRNA reduction in participants consenting to pre- and post-treatment tumor biopsies.


Enrollment: 43
Study Start Date: June 2014
Study Completion Date: July 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: TKM-080301
TKM-080301 intravenous infusion
Other Name: PLK1-HCC

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Child-Pugh class of A
  • 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

Key Exclusion Criteria:

  • History of significant cardiovascular disease will be excluded
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02191878

Locations
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
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada
China
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
Singapore
National University Hospital
Singapore, Singapore
Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Medical University Hospital, Shuang-Ho Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Sponsors and Collaborators
Arbutus Biopharma Corporation
Investigators
Study Director: Mark Kowalski, M.D., Ph.D. Tekmira Pharmaceuticals
  More Information

Responsible Party: Arbutus Biopharma Corporation
ClinicalTrials.gov Identifier: NCT02191878     History of Changes
Other Study ID Numbers: TKM-HCC-001 
Study First Received: July 9, 2014
Last Updated: July 20, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Arbutus Biopharma Corporation:
Liver Cancer
Liver Neoplasms
Liver Epithelial Neoplasms
Liver Cancer, malignant

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 29, 2016