Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma
Conditions
Hepatocellular Carcinoma - Hepatoma - Liver Cancer, Adult - Liver Cell Carcinoma, Adult
Conditions: official terms
Carcinoma - Carcinoma, Hepatocellular - Liver Neoplasms
Conditions: Keywords
Liver Cancer, Liver Neoplasms, Liver Epithelial Neoplasms, Liver Cancer, malignant
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: TKM-080301
Type: Drug
Overall Status
Recruiting
Summary
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
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
Arizona Clinical Research Center
Tucson, Arizona, United States
Status: Recruiting
Contact: Patricia Plezia, D. Pharm - 520-290-8830 - pplezia@accresearch.com
University of California San Francisco
San Francisco, California, United States
Status: Recruiting
Contact: Christina Chun - 415-353-4084 - chunc@cc.ucsf.edu
Kansas City Research Institute
Kansas City, Missouri, United States
Status: Recruiting
Contact: Karen Muehlebach, RN, BSN - 816-361-0055 - kmuehlebach@kcresearchinstitute.com
Memorial Sloan Kettering Cancer Center
New york, New York, United States
Status: Recruiting
Mary Crowley Cancer Research Centers
Dallas, Texas, United States
Status: Recruiting
Contact: Ashley Barnett - 214-658-1987 - Abarnett@marycrowley.org
Princess Margaret Hospital
Toronto, Ontario, Canada
Status: Recruiting
Queen Mary Hospital
Hong Kong, China
Status: Recruiting
ASAN Medical Center
Seoul, Gyeonggi-do, Korea, Republic of
Status: Recruiting
Contact: Young Ae Kang - +82 2 3010 7732 - kangya@amc.seoul.kr
Samsung Medical Center
Seoul, Gyeonggi-do, Korea, Republic of
Status: Recruiting
Contact: YoonJeong Ahn - 82221487395 - younjeong.ahn@samsung.com
Seoul National University Hospital
Seoul, Gyeonggi-do, Korea, Republic of
Status: Recruiting
Contact: JinHee Kim - 8227408111 - dadas3178@naver.com
Severence Hospital, Yonsei, University Health System
Seoul, Korea, Republic of
Status: Recruiting
National University Hospital
Singapore, Singapore
Status: Recruiting
National Taiwan University Hospital
Taipei, Taiwan
Status: Recruiting
Taipei Medical University Hospital, Shuang-Ho Hospital
Taipei, Taiwan
Status: Recruiting
Taipei Veterans General Hospital
Taipei, Taiwan
Status: Recruiting
Start Date
June 2014
Completion Date
April 2016
Sponsors
Tekmira Pharmaceuticals Corporation
Source
Tekmira Pharmaceuticals Corporation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page