Clinical Trials List
Protocol Number104-13-302
2014-07-01 - 2022-12-31
Phase III
Terminated4
Study ended1
ICD-10C22.0
Liver cell carcinoma
ICD-9155.0
Malignant neoplasm of liver, primary
A Phase III, Randomized, Double Blind, Dummy-Controlled Study of ThermoDox® (Lyso-Thermosensitive Liposomal DoxorubicinLTLD) in Hepatocellular Carcinoma (HCC) using standardized Radiofrequency Ablation (RFA) treatment time ≥ 45 minutes for solitary lesions ≥ 3 cm to ≤ 7 cm.
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Trial Applicant
Syneos Health
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Sponsor
Celsion Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- 余健鈞 Digestive System Department
- JA-DER LIANG Digestive System Department
- 謝宏仁 Division of Radiology
- Shih-Jer Hsu Digestive System Department
- 黃冠棠 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- CHUNG-HSIN CHANG Digestive System Department
- 鄭紹彬 Division of General Surgery
- 李少武 Digestive System Department
- Sheng-Shun Yang Digestive System Department
- 鄭友琦 Division of Radiology
- 葉宏仁 Digestive System Department
- 呂宜達 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Pin-Nan Cheng Digestive System Department
- 吳毅晉 Digestive System Department
- 邱彥程 Digestive System Department
- Liu Yi-Sheng Division of Radiology
- Chiu Hung Chiu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- YING-CHI TSENG Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Po-Heng Chuang Digestive System Department
- 陳昇弘 Digestive System Department
- 蘇文邦 Digestive System Department
- Hung-Yao Chen Digestive System Department
- Hsueh-Chou Lai Digestive System Department
Condition/Disease
Hepatocellular Carcinoma (HCC)
Objectives
The primary objective is to compare overall survival (OS) between patients receiving
RFA plus ThermoDox versus RFA alone, using a standardized Radiofrequency
Ablation (sRFA) treatment dwell time ≥ 45 minutes.
The secondary objectives are to compare progression-free survival (PFS) and safety
between patients receiving sRFA plus ThermoDox versus sRFA alone, using a
standardized treatment dwell time ≥ 45 minutes.
Test Drug
ThermoDox® (Lyso-Thermosensitive Liposomal Doxorubicin)
Active Ingredient
Doxorubicin HCl
Dosage Form
Injection
Dosage
2 mg/ml
Endpoints
Primary Endpoint: Survival
All patients will be monitored for survival by recording their visits during routine follow up
for response to treatment. The visits are scheduled to occur every four months from the first
imaging study confirming complete ablation until month 25 or radiological progression,
whichever comes first. If patients have not demonstrated radiological progression at month
25 then the imaging visit schedule is reduced to every six months until progression.
Survival is confirmed at every imaging visit.
Once radiological progression is confirmed then follow up for overall survival is required.
Sites are required to confirm contact with the subject during either a clinic visit or a
telephone contact every three months. It is expected that subject follow up will be about five
years.
Secondary Endpoint: Progression Free Survival
The protocol incorporates modified RECIST (mRECIST) developed for HCC clinical
research as a basis to evaluate tumor response. The mRECIST enables assessment of overall
response by taking into account target lesion response, and presence or absence of new
lesions. A separate imaging manual and imaging training program has been developed for
this study in order to ensure uniformity in imaging technique and imaging review in
accordance with mRECIST.
All patients will be monitored for survival by recording their visits during routine follow up
for response to treatment. The visits are scheduled to occur every four months from the first
imaging study confirming complete ablation until month 25 or radiological progression,
whichever comes first. If patients have not demonstrated radiological progression at month
25 then the imaging visit schedule is reduced to every six months until progression.
Survival is confirmed at every imaging visit.
Once radiological progression is confirmed then follow up for overall survival is required.
Sites are required to confirm contact with the subject during either a clinic visit or a
telephone contact every three months. It is expected that subject follow up will be about five
years.
Secondary Endpoint: Progression Free Survival
The protocol incorporates modified RECIST (mRECIST) developed for HCC clinical
research as a basis to evaluate tumor response. The mRECIST enables assessment of overall
response by taking into account target lesion response, and presence or absence of new
lesions. A separate imaging manual and imaging training program has been developed for
this study in order to ensure uniformity in imaging technique and imaging review in
accordance with mRECIST.
Inclution Criteria
1. Male or female ≥ 18 years of age.
2. Diagnosed with a single HCC lesion ≥ 3.0 cm but ≤ 7.0 cm in maximum
diameter based on diagnosis at screening.
Subjects meeting the American Association for the Study of Liver Disease
(AASLD) criteria may be randomized without a biopsy, but will undergo a
biopsy during the RFA procedure unless contraindicated or unattainable.
Subjects not meeting the AASLD criteria for HCC will need a biopsy to
confirm HCC prior to randomization.
3. Be an appropriate candidate for receiving RFA as a medically indicated
treatment as evaluated by the following factors:
The position and accessibility of the target lesion allows for the safe
administration of multiple ablation cycles or deployments to achieve a probe
dwell time of ≥ 45 minutes.
Not a candidate for surgical resection according to the local guidelines for
resection and in the Investigator’s judgment.
4. Child-Pugh Class A without either current encephalopathy or ascites.
5. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
6. ECOG performance status 0.
7. Willing to sign an informed consent form, indicating awareness of the
investigational nature of this study that is in keeping with the policies of the
institution.
2. Diagnosed with a single HCC lesion ≥ 3.0 cm but ≤ 7.0 cm in maximum
diameter based on diagnosis at screening.
Subjects meeting the American Association for the Study of Liver Disease
(AASLD) criteria may be randomized without a biopsy, but will undergo a
biopsy during the RFA procedure unless contraindicated or unattainable.
Subjects not meeting the AASLD criteria for HCC will need a biopsy to
confirm HCC prior to randomization.
3. Be an appropriate candidate for receiving RFA as a medically indicated
treatment as evaluated by the following factors:
The position and accessibility of the target lesion allows for the safe
administration of multiple ablation cycles or deployments to achieve a probe
dwell time of ≥ 45 minutes.
Not a candidate for surgical resection according to the local guidelines for
resection and in the Investigator’s judgment.
4. Child-Pugh Class A without either current encephalopathy or ascites.
5. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
6. ECOG performance status 0.
7. Willing to sign an informed consent form, indicating awareness of the
investigational nature of this study that is in keeping with the policies of the
institution.
Exclusion Criteria
1. Is scheduled for liver transplantation
2. Expected ablation volume > 30% of total liver volume or removal of 3 hepatic
segments
3. More than 1 lesion identified during baseline.
4. Have previously received therapeutic treatment for HCC outside the study
protocol or is expected to receive concomitant HCC treatment prior to PFS
event.
5. Have serious medical illnesses including, but not limited to, congestive heart
failure, myocardial infarction or cerebral vascular accident within the last six
months, or life threatening cardiac arrhythmias.
6. Have previously received any anthracycline outside the protocol
7. Have extrahepatic metastasis.
8. Have portal or hepatic vein tumor invasion/thrombosis.
9. Have body temperature >101ºF (38.3ºC) immediately prior to study treatment.
10. Baseline laboratories (repeat lab tests are permitted to evaluate eligibility during
the Screening Period. Lab results must be within protocol range prior to study
treatment.)
• Absolute neutrophil count < 1500/mm3
• Platelet count < 75,000/mm3
• Hgb < 10.0 g/dL (unless the hemoglobin value has been stable, the subject
is cardiovascularly stable, asymptomatic and judged able to withstand the
RFA procedure)
Note: If clinically indicated, subjects may receive platelets or packed RBC
transfusions and be re-evaluated after condition is treated.
11. Baseline Chemistry
• Serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl)
≤25.0 mL/min.
• Serum bilirubin > 3.0 mg/dL.
• Serum albumin < 2.8 g/dL.
12. Have any known allergic reactions to any of the drugs or liposomal components
or intravenous imaging agents that prohibit the ability to complete the imaging
requirements.
13. Are pregnant or breast-feeding. In women of childbearing potential, a negative
serum pregnancy test is required prior to study treatment.
14. Women of childbearing potential and men who are not practicing an acceptable
form of birth control (i.e. diaphragm, cervical cap, condom, surgical sterility or
birth control pills. Women whose partner has or men who have undergone a
vasectomy must use a second form of birth control).
15. Have INR > 1.5 times the institution’s upper normal limit (UNL), except in
subjects who are therapeutically anticoagulated for medical conditions unrelated
to HCC such as atrial fibrillation. Subjects may be re-screened after condition is
treated or anticoagulant is withheld.
16. Have contraindications to receiving doxorubicin HCl.
17. Are being treated with other investigational agents.
18. Use of an investigational drug outside this study within 30 days or 5 half-lives,
whichever is longer, preceding the first dose of study medication.
19. Have other concurrent malignancy (subjects with treated squamous cell
carcinoma of the skin or basal cell carcinoma of the skin may be included),
evidence of extrahepatic cancer from their primary malignancy, or ongoing,
medically significant active infection.
20. HIV positive.
21. NYHA class III or IV functional classification for heart failure.
22. Evidence of hemachromatosis.
2. Expected ablation volume > 30% of total liver volume or removal of 3 hepatic
segments
3. More than 1 lesion identified during baseline.
4. Have previously received therapeutic treatment for HCC outside the study
protocol or is expected to receive concomitant HCC treatment prior to PFS
event.
5. Have serious medical illnesses including, but not limited to, congestive heart
failure, myocardial infarction or cerebral vascular accident within the last six
months, or life threatening cardiac arrhythmias.
6. Have previously received any anthracycline outside the protocol
7. Have extrahepatic metastasis.
8. Have portal or hepatic vein tumor invasion/thrombosis.
9. Have body temperature >101ºF (38.3ºC) immediately prior to study treatment.
10. Baseline laboratories (repeat lab tests are permitted to evaluate eligibility during
the Screening Period. Lab results must be within protocol range prior to study
treatment.)
• Absolute neutrophil count < 1500/mm3
• Platelet count < 75,000/mm3
• Hgb < 10.0 g/dL (unless the hemoglobin value has been stable, the subject
is cardiovascularly stable, asymptomatic and judged able to withstand the
RFA procedure)
Note: If clinically indicated, subjects may receive platelets or packed RBC
transfusions and be re-evaluated after condition is treated.
11. Baseline Chemistry
• Serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl)
≤25.0 mL/min.
• Serum bilirubin > 3.0 mg/dL.
• Serum albumin < 2.8 g/dL.
12. Have any known allergic reactions to any of the drugs or liposomal components
or intravenous imaging agents that prohibit the ability to complete the imaging
requirements.
13. Are pregnant or breast-feeding. In women of childbearing potential, a negative
serum pregnancy test is required prior to study treatment.
14. Women of childbearing potential and men who are not practicing an acceptable
form of birth control (i.e. diaphragm, cervical cap, condom, surgical sterility or
birth control pills. Women whose partner has or men who have undergone a
vasectomy must use a second form of birth control).
15. Have INR > 1.5 times the institution’s upper normal limit (UNL), except in
subjects who are therapeutically anticoagulated for medical conditions unrelated
to HCC such as atrial fibrillation. Subjects may be re-screened after condition is
treated or anticoagulant is withheld.
16. Have contraindications to receiving doxorubicin HCl.
17. Are being treated with other investigational agents.
18. Use of an investigational drug outside this study within 30 days or 5 half-lives,
whichever is longer, preceding the first dose of study medication.
19. Have other concurrent malignancy (subjects with treated squamous cell
carcinoma of the skin or basal cell carcinoma of the skin may be included),
evidence of extrahepatic cancer from their primary malignancy, or ongoing,
medically significant active infection.
20. HIV positive.
21. NYHA class III or IV functional classification for heart failure.
22. Evidence of hemachromatosis.
The Estimated Number of Participants
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Taiwan
75 participants
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Global
550 participants
