Clinical Trials List
Protocol NumberTKM-HCC-001
NCT Number(ClinicalTrials.gov Identfier)NCT02191878
2014-12-30 - 2016-05-01
Phase I/II
Terminated3
ICD-10C22.0
Liver cell carcinoma
AN 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
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Tekmira Pharmaceuticals Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wei-Hong Cheng Division of Hematology & Oncology
- 謝瑞坤 Division of Hematology & Oncology
- Tsu-Yi Chao Division of Hematology & Oncology
- JENG-FONG CHIOU Division of Hematology & Oncology
- 夏和雄 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Huang Chen Division of Hematology & Oncology
- Yee Chao Division of Radiation Therapy
- Rheun-Chuan Lee Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林宗哲 Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Hepatocellular Carcinoma (HCC)
Objectives
Primary
Assessment of the safety, tolerability, and pharmacokinetic (PK)
profile of TKM-080301 in hepatocellular carcinoma (HCC)
Secondary
Preliminary assessment of anti-tumor activity
Assessment of clinical benefit in the expansion cohort
Test Drug
TKM 080301
Active Ingredient
TKM 080301
Dosage Form
Vial
Dosage
5ml
Endpoints
Primary
Maximum tolerated dose (MTD)
Laboratory assessments, cytokine levels, vital signs, physical
examinations, and electrocardiograms (ECG)
Serial PK sampling during Cycles 1 and Cycle 2
Secondary
Response Evaluation Criteria In Solid Tumors version 1.1
(RECIST 1.1) assessment by computed tomography (CT) /
magnetic resonance imaging (MRI) after every 2 cycles.
Clinical benefit rate in the expansion cohort, defined as the sum
of: RECIST 1.1-defined complete response (CR), plus
RECIST 1.1 partial response (PR), plus minor response (MR)
(≥20% decrease of target tumors but <30% decrease), plus
RECIST 1.1 stable disease (SD) lasting ≥16 weeks, plus ≥50%
decrease in AFP from baseline.
Maximum tolerated dose (MTD)
Laboratory assessments, cytokine levels, vital signs, physical
examinations, and electrocardiograms (ECG)
Serial PK sampling during Cycles 1 and Cycle 2
Secondary
Response Evaluation Criteria In Solid Tumors version 1.1
(RECIST 1.1) assessment by computed tomography (CT) /
magnetic resonance imaging (MRI) after every 2 cycles.
Clinical benefit rate in the expansion cohort, defined as the sum
of: RECIST 1.1-defined complete response (CR), plus
RECIST 1.1 partial response (PR), plus minor response (MR)
(≥20% decrease of target tumors but <30% decrease), plus
RECIST 1.1 stable disease (SD) lasting ≥16 weeks, plus ≥50%
decrease in AFP from baseline.
Inclution Criteria
Inclusion Criteria
To be eligible for the study, subjects must fulfill all of the following criteria:
1. Men or women ≥18 years of age in the US and Canada, or the appropriate age of consent
in other jurisdictions.
2. Histologically or cytologically confirmed metastatic or locally advanced inoperable HCC.
3. Local therapy for HCC, including surgical resection, has failed or is not feasible. Subjects
may have received prior systemic therapy for HCC.
4. Life expectancy ≥3 months.
5. At least 1 measurable lesion by RECIST 1.1 criteria.
6. Child-Pugh class of A5 or A6 (APPENDIX G).
7. Eastern Co-operative Oncology Group (ECOG) performance status of 0 to 1.
8. Aspartate aminotransferase (AST) ≤5.0 × ULN.
9. Alanine aminotransferase (ALT) ≤5.0 × ULN.
10. Total bilirubin ≤3.0 mg/dL.
11. Albumin ≥2.8 g/dL.
12. Hemoglobin ≥8.5 g/dL without transfusion in the previous 4 weeks.
13. Platelets ≥75,000 /mL.
14. Absolute neutrophil count (ANC) ≥1,200 /mL
15. Serum creatinine ≤1.5 × ULN.
16. International normalized ratio (INR) ≤1.7.
17. Female subjects of child-bearing potential must not be pregnant or lactating, must have a
negative pregnancy test at Screening and must be practicing an adequate method of birth
control. Acceptable methods of birth control include use of an intrauterine device (IUD),
oral, implanted or injected contraceptives, and barrier methods with spermicide.
18. Subjects must sign an informed consent form (ICF) that complies with appropriate
regulations for the US e.g., US 21 Code of Federal regulations [CFR] 50, or appropriate
regulations for jurisdictions other than the US, and the International Conference on
Harmonization (ICH) guidelines prior to undergoing any study-related procedures.
To be eligible for the study, subjects must fulfill all of the following criteria:
1. Men or women ≥18 years of age in the US and Canada, or the appropriate age of consent
in other jurisdictions.
2. Histologically or cytologically confirmed metastatic or locally advanced inoperable HCC.
3. Local therapy for HCC, including surgical resection, has failed or is not feasible. Subjects
may have received prior systemic therapy for HCC.
4. Life expectancy ≥3 months.
5. At least 1 measurable lesion by RECIST 1.1 criteria.
6. Child-Pugh class of A5 or A6 (APPENDIX G).
7. Eastern Co-operative Oncology Group (ECOG) performance status of 0 to 1.
8. Aspartate aminotransferase (AST) ≤5.0 × ULN.
9. Alanine aminotransferase (ALT) ≤5.0 × ULN.
10. Total bilirubin ≤3.0 mg/dL.
11. Albumin ≥2.8 g/dL.
12. Hemoglobin ≥8.5 g/dL without transfusion in the previous 4 weeks.
13. Platelets ≥75,000 /mL.
14. Absolute neutrophil count (ANC) ≥1,200 /mL
15. Serum creatinine ≤1.5 × ULN.
16. International normalized ratio (INR) ≤1.7.
17. Female subjects of child-bearing potential must not be pregnant or lactating, must have a
negative pregnancy test at Screening and must be practicing an adequate method of birth
control. Acceptable methods of birth control include use of an intrauterine device (IUD),
oral, implanted or injected contraceptives, and barrier methods with spermicide.
18. Subjects must sign an informed consent form (ICF) that complies with appropriate
regulations for the US e.g., US 21 Code of Federal regulations [CFR] 50, or appropriate
regulations for jurisdictions other than the US, and the International Conference on
Harmonization (ICH) guidelines prior to undergoing any study-related procedures.
Exclusion Criteria
Exclusion Criteria
Subjects meeting any of the following criteria will be excluded from the study:
1. History of significant cardiovascular disease e.g., uncontrolled hypertension in the
previous 4 weeks or a prior history of angina, congestive heart failure, myocardial
infarction, or serious cardiac arrhythmia. Subjects with New York Heart Association
Functional Classification of Class II or greater will be excluded (APPENDIX H).
2. History of liver transplant.
3. Diagnosis of fibrolamellar HCC or tumors of mixed histology.
4. Subjects known to be positive for Human immunodeficiency virus (HIV) infection.
5. Known central nervous system (CNS) or brain metastases.
6. Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently
than once every 3 months.
7. Symptomatic encephalopathy within 3 months prior to the first dose of TKM-080301
and/or requirement for medication for encephalopathy.
8. Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.
9. Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.
10. Subjects with a HBV DNA test result ≥10,000 IU/mL are excluded, unless they respond
to treatment for HBV as described in Section 9.3.7.8. Subjects with a HBV DNA test
result <10,000 IU/mL must be receiving a treatment regimen including nucleos(t)ide
analog(s).
11. Receiving current systemic anti-viral therapy for HCV. See Section 9.3.7.8.
12. Treatment within 2 weeks prior to the first dose of TKM-080301 with anticoagulant or
thrombolytic treatment.
13. Any of the following within 4 weeks prior to the first dose of TKM-080301:
a. Major surgery
b. Loco-regional therapy for HCC
14. Radiotherapy within 3 weeks prior to the first dose of TKM-080301. Localized palliative
radiotherapy is permissible at any time, but should be discussed with the Medical
Monitor.
15. Prior chemotherapy within 3 weeks prior to the first dose of TKM-080301.
16. Prior therapy with nitrosoureas or mitomycin within 6 weeks prior to the first dose of
TKM-080301.
17. Prior therapy with any biologic chemotherapeutic or investigational drug within 5 halflives or 3 weeks, whichever is longer prior to the first dose of TKM-080301.
18. Tumor biopsy within 1 week prior to the first dose of TKM-080301.
19. Any severe concurrent disease including significant inflammatory conditions or
infections, or significant unresolved toxicities (>Grade 1) related to previous treatment,
which in the judgment of the Investigator, would make the subject inappropriate for study
participation.
Subjects meeting any of the following criteria will be excluded from the study:
1. History of significant cardiovascular disease e.g., uncontrolled hypertension in the
previous 4 weeks or a prior history of angina, congestive heart failure, myocardial
infarction, or serious cardiac arrhythmia. Subjects with New York Heart Association
Functional Classification of Class II or greater will be excluded (APPENDIX H).
2. History of liver transplant.
3. Diagnosis of fibrolamellar HCC or tumors of mixed histology.
4. Subjects known to be positive for Human immunodeficiency virus (HIV) infection.
5. Known central nervous system (CNS) or brain metastases.
6. Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently
than once every 3 months.
7. Symptomatic encephalopathy within 3 months prior to the first dose of TKM-080301
and/or requirement for medication for encephalopathy.
8. Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.
9. Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.
10. Subjects with a HBV DNA test result ≥10,000 IU/mL are excluded, unless they respond
to treatment for HBV as described in Section 9.3.7.8. Subjects with a HBV DNA test
result <10,000 IU/mL must be receiving a treatment regimen including nucleos(t)ide
analog(s).
11. Receiving current systemic anti-viral therapy for HCV. See Section 9.3.7.8.
12. Treatment within 2 weeks prior to the first dose of TKM-080301 with anticoagulant or
thrombolytic treatment.
13. Any of the following within 4 weeks prior to the first dose of TKM-080301:
a. Major surgery
b. Loco-regional therapy for HCC
14. Radiotherapy within 3 weeks prior to the first dose of TKM-080301. Localized palliative
radiotherapy is permissible at any time, but should be discussed with the Medical
Monitor.
15. Prior chemotherapy within 3 weeks prior to the first dose of TKM-080301.
16. Prior therapy with nitrosoureas or mitomycin within 6 weeks prior to the first dose of
TKM-080301.
17. Prior therapy with any biologic chemotherapeutic or investigational drug within 5 halflives or 3 weeks, whichever is longer prior to the first dose of TKM-080301.
18. Tumor biopsy within 1 week prior to the first dose of TKM-080301.
19. Any severe concurrent disease including significant inflammatory conditions or
infections, or significant unresolved toxicities (>Grade 1) related to previous treatment,
which in the judgment of the Investigator, would make the subject inappropriate for study
participation.
The Estimated Number of Participants
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Taiwan
12 participants
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Global
38 participants
