NCT02191878

Brief 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

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
43

participants targeted

Target at P50-P75 for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started Jun 2014

Shorter than P25 for phase_1 hepatocellular-carcinoma

Geographic Reach
6 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2014

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 9, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 16, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

January 16, 2019

Status Verified

January 1, 2019

Enrollment Period

1.9 years

First QC Date

July 9, 2014

Last Update Submit

January 14, 2019

Conditions

Hepatocellular CarcinomaHepatomaLiver Cancer, AdultLiver Cell Carcinoma, Adult

Keywords

Liver CancerLiver NeoplasmsLiver Epithelial NeoplasmsLiver Cancer, malignant

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD)

    Laboratory assessments

    Up to 6 months after initial dose.

Secondary Outcomes (2)

  • Preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)

    Upon every 2 cycles of treatment for up to 6 months

  • Clinical Benefit Rate at maximum tolerated dose (MTD) in Expansion Cohort

    Upon completion of treatment of expansion cohort; up to 6 months after last participant is dosed.

Other Outcomes (1)

  • Assessment of Pharmacodynamic Effect

    Upon completion of cycle 1 and cycle 2 treatment; 1 and 2 months after last participant is dosed in expansion cohort.

Study Arms (1)

Phase 1 Escalation / Phase 2 Expansion

EXPERIMENTAL

Phase 1 - dose escalation with intravenous infusion of TKM-080301 to determine MTD. Phase 2 - dose expansion at the MTD.

Drug: TKM-080301

Interventions

TKM-080301DRUG

TKM-080301 intravenous infusion

Also known as: PLK1-HCC
Phase 1 Escalation / Phase 2 Expansion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Arizona Clinical Research Center

Tucson, Arizona, 85715, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Queen Mary Hospital

Hong Kong, China

Location

National University Hospital

Singapore, Singapore

Location

Seoul National University Hospital

Seoul, Gyeonggi-do, 110744, South Korea

Location

Samsung Medical Center

Seoul, Gyeonggi-do, 135-710, South Korea

Location

ASAN Medical Center

Seoul, Gyeonggi-do, 138-736, South Korea

Location

Severence Hospital, Yonsei, University Health System

Seoul, South Korea

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Medical University Hospital, Shuang-Ho Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Related Publications (1)

  • 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.

    PMID: 30598500DERIVED

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Interventions

TKM-080301

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Study Officials

  • Mark Kowalski, M.D., Ph.D.

    Tekmira Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 9, 2014

First Posted

July 16, 2014

Study Start

June 1, 2014

Primary Completion

May 1, 2016

Study Completion

July 1, 2016

Last Updated

January 16, 2019

Record last verified: 2019-01

Locations

US(5)CA(1)CN(1)SG(1)KR(4)TW(3)