Hepatocellular CarcinomaPhase 1/2NCT02191878
Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing TKM-080301 in people with Hepatocellular Carcinoma and Hepatoma, run by Arbutus Biopharma Corporation at 15 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult
- What is being tested?
- TKM-080301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 15 sitesin 6 countries
- Study dates
- Jun 2014to Jul 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
United States5 sites
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230
Kansas City Research Institute
Kansas City, Missouri, 64131
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California San Francisco
San Francisco, California, 94115
Arizona Clinical Research Center
Tucson, Arizona, 85715
South Korea4 sites
Seoul National University Hospital
Seoul, Gyeonggi-do, 110744
Samsung Medical Center
Seoul, Gyeonggi-do, 135-710
ASAN Medical Center
Seoul, Gyeonggi-do, 138-736
Severence Hospital, Yonsei, University Health System
Seoul
Taiwan3 sites
National Taiwan University Hospital
Taipei
Taipei Medical University Hospital, Shuang-Ho Hospital
Taipei
Taipei Veterans General Hospital
Taipei
About this study
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
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
Read the 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.
- Being tested
- TKM-080301
- Keywords
- Liver Cancer, Liver Neoplasms, Liver Epithelial Neoplasms, Liver Cancer, malignant
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKM-080301Drug
Also called PLK1-HCC
TKM-080301 intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: TKM-080301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Laboratory assessments
Measured: 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)
Obtain preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
Measured: Upon every 2 cycles of treatment for up to 6 months
Clinical Benefit Rate at maximum tolerated dose (MTD) in Expansion Cohort
Assessed after completion of Phase 2.
Measured: Upon completion of treatment of expansion cohort; up to 6 months after last participant is dosed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startJun 2014
- Primary completionMay 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arbutus Biopharma Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Kowalski, M.D., Ph.D., Study director, Tekmira Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02191878
- Sponsor's protocol ID
- TKM-HCC-001
- Status last verified
- Jan 2019
- First submitted
- 9 Jul 2014
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30598500
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02191878
- Acronym / sponsor ID
- TKM-HCC-001
- Keywords
- Liver Cancer, Liver Neoplasms, Liver Epithelial Neoplasms, Liver Cancer, malignant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Arbutus Biopharma CorporationIndustry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- May 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 16 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Escalation / Phase 2 Expansion | Experimental | Drug: TKM-080301Phase 1 - dose escalation with intravenous infusion of TKM-080301 to determine MTD. Phase 2 - dose expansion at the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TKM-080301Also: PLK1-HCCTKM-080301 intravenous infusion | Drug | Phase 1 Escalation / Phase 2 Expansion |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Up to 6 months after initial dose.
Laboratory assessments
2 secondary outcomes
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
- Derived from this study: PubMed 30598500El 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Kowalski, M.D., Ph.D. study director
Tekmira Pharmaceuticals
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TKM-080301 in people with Hepatocellular Carcinoma and Hepatoma, run by Arbutus Biopharma Corporation at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, South Korea, Taiwan, Canada, China and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: Up to 6 months after initial dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02191878, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2019.