Localized Hepatocellular Carcinoma
Conditions
Brief summary
A Single-arm Trial of Transcatheter Arterial Chemoembolization with Tandem Microspheres in the Treatment of Localized Hepatocellular Carcinoma
Detailed description
It is a prospective, single-arm, multicenter study. The primary effectiveness endpoint for this clinical trial is 6-month overall objective tumor response (ORR).
Interventions
DEVICETandem Microsphere loaded with Epirubicin
The primary objective of this study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization with Tandem Microspheres loaded with Epirubicin in the treatment of patients with localized hepatocellular carcinoma (HCC)
Sponsors
Varian Medical Systems
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is able to provide informed consent and must sign the Institutional Review Board/Ethics Committee (IRB/EC) approved Informed Consent Form. 2. Male or female of age ≥18 and ≤75 years. 3. Confirmed diagnosis of HCC according to the diagnostic criteria included in the management guideline issued by China's Ministry of Health in 2017. 4. HCC is diagnosed for the first time or recurrence of tumor after surgical or ablation treatment. 5. Single tumor less than 7cm in diameter or multiple tumors with maximum 3 lesions with \>1cm in diameter, individual diameter \<7cm and less than 10cm in total diameter. 6. no previous chemotherapy, radiotherapy or transarterial embolization (with or without chemotherapy) for HCC 7. Preserved liver function (Child-Pugh A or B7). 8. ECOG Performance Status 0 or 1.
Exclusion criteria
1. Presence of vascular invasion or extra-hepatic spread of disease, or diffuse HCC, defined as \>50% liver involvement , or arteriovenuous fistula 2. Macrovascular invasion of main or primary branches of portal vein at entry into the study 3. Any contraindication for TACE treatment 4. Any contraindication for Epirubicin administration 5. Advanced liver disease (bilirubin levels \>2 mg/dl, AST or ALT \>5 times upper limit of normal) 6. Renal failure or insufficient renal function (Creatinine levels \>2 mg/dl) 7. Subject unable to receive MRI examination 8. Pregnant or breast feeding woman, or plan to become pregnant during treatment or within 12 months of treatment 9. couldn't commit reliable birth control measures during treatment or within 12 months of treatment 10. Subject is participating other investigational drug or device clinical trial within 30 days of signing the informed consent 11. Subject is not suitable to participate in the study as judged by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Tumor Response at 6 Months by MRI (Magnetic Resonance Imaging) | At 6 months | The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Tumor Response at 30-day | At 1month | The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart. |
| Kaplan-Meier Analyses the Percent of Participants for PPF(Proportion Progression-Free) at 12 Months | from first TACE to 12 months | Kaplan-Meier analyses the percent of participants for PPF which is defined as the length of time from the treatment initiation, that treated subjects are still progression-free. EASL and mRECIST response assessment of target lesion for HCC. The data items to be captured will include: * The date of the disease progression in the Overall Response form * The very last date by scanning all available dates in the database * The desired cut-off days The proportion of any time point will be determined by the Kaplan-Meier estimates. |
| Kaplan-Meier Analyses the Percent of Participants for Overall Survival | from first TACE to 12 months | Kaplan-Meier analyses the percent of participants for Overall survival which is defined as the length of time from the treatment initiation, that treated subjects are still alive. The Kaplan-Meier analysis is aimed to capture the all-cause death for each subject. Subjects who are lost-to-follow will be considered being censored. There are three critical data items to be captured: * Death date * The very last date in the database (e.g. follow-up visit date and/or site reported AE date) * The desired cut-off days (e.g. 6-month OS at 182 days, 12-month OS at 365 days) In addition to the Kaplan-Meier survival curve, the median survival time (mOS) will also be used to represent the study cohort. |
| Kaplan-Meier Analyses the Percent of Participants for Time to Progression (TTP) at 12 Months | At 12 months | Kaplan-Meier analyses the percent of participants for TTP which is defined as the length of time from the treatment initiation to either the date of the first disease progression occurred, as assessed by the investigators, or the date of the subject died due to any cause, whichever comes earlier. EASL and mRECIST response assessment of target lesion for HCC. TTP (also referred as time to treatment failure) will be measured by a few data items list below: * The date of the disease progression in the Overall Response form * The date of lost-to-follow due to: * Adverse events * Progressive disease/insufficient therapeutic response * Death * Failure to return * Refusing treatment/being unwilling to cooperate/withdrawing consent * The very last date by scanning all available dates in the database * The desired cut-off days |
| Number of Participants With Objective Tumor Response at 3 Months | At 3 months | The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart. |
| Kaplan-Meier Analyses the Percent of Participants for Time to Extrahepatic Spread | At 12 month | Kaplan-Meier analyses the percent of participants for Time to Extrahepatic Spread which the length of time from the treatment initiation to the development of extrahepatic spread of the disease via imaging assessment. The data items to be considered will include: * The date of the extrahepatic spread in the Overall Response form * The very last date by scanning all available dates in the database * The desired cut-off days |
| Number of Adverse Events Relate to Study Device in 12 Months Post Procedure | in 12 months | Number and documents of adverse events relate to study device in 12 months post procedure |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single -Arm A Single-arm Trial of Transcatheter Arterial Chemoembolization with Tandem Microspheres in the Treatment of Localized Hepatocellular Carcinoma
Tandem Microsphere loaded with Epirubicin: The primary objective of this study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization with Tandem Microspheres loaded with Epirubicin in the treatment of patients with localized hepatocellular carcinoma (HCC) | 109 |
| Total | 109 |
Baseline characteristics
| Characteristic | Single -Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 42 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants |
| Age, Continuous | 60.22 years STANDARD_DEVIATION 8.67 |
| Child-Pugh Score Class A | 97 Participants |
| Child-Pugh Score Class B | 11 Participants |
| Disease History Cirrhosis | 74 Participants |
| Disease History Diabetes | 16 Participants |
| Disease History Hepatitis B | 90 Participants |
| Disease History Hepatitis C | 8 Participants |
| Disease History Hypertension | 25 Participants |
| ECOG Performance Status 0 Score | 97 Participants |
| ECOG Performance Status 1 Score | 11 Participants |
| Race/Ethnicity, Customized Han of Chinese | 108 Participants |
| Region of Enrollment China | 108 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 108 |
| other Total, other adverse events | 75 / 108 |
| serious Total, serious adverse events | 13 / 108 |
Outcome results
Primary
Number of Participants With Objective Tumor Response at 6 Months by MRI (Magnetic Resonance Imaging)
The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart.
Time frame: At 6 months
Population: Total enrolled 109 subjects , 7 subjects were not completed 6 months primary endpoint follow up visit and were not included in the per protocol group for analysis. So overall Number of Participants Analyzed were 102.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single -Arm | Number of Participants With Objective Tumor Response at 6 Months by MRI (Magnetic Resonance Imaging) | 6-month ORR (EASL criteria) | 75 participants |
| Single -Arm | Number of Participants With Objective Tumor Response at 6 Months by MRI (Magnetic Resonance Imaging) | 6-month ORR (mRECIST criteria) | 73 participants |
Secondary
Kaplan-Meier Analyses the Percent of Participants for Overall Survival
Kaplan-Meier analyses the percent of participants for Overall survival which is defined as the length of time from the treatment initiation, that treated subjects are still alive. The Kaplan-Meier analysis is aimed to capture the all-cause death for each subject. Subjects who are lost-to-follow will be considered being censored. There are three critical data items to be captured: * Death date * The very last date in the database (e.g. follow-up visit date and/or site reported AE date) * The desired cut-off days (e.g. 6-month OS at 182 days, 12-month OS at 365 days) In addition to the Kaplan-Meier survival curve, the median survival time (mOS) will also be used to represent the study cohort.
Time frame: from first TACE to 12 months
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment, 1 subject withdrew consent from study participation at 6 month, 1 subject withdrew consent from study participation at 12 month. All 3 subjects are not included in the group for overall survival analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for Overall Survival | 100 Percent of participants |
Secondary
Kaplan-Meier Analyses the Percent of Participants for PPF(Proportion Progression-Free) at 12 Months
Kaplan-Meier analyses the percent of participants for PPF which is defined as the length of time from the treatment initiation, that treated subjects are still progression-free. EASL and mRECIST response assessment of target lesion for HCC. The data items to be captured will include: * The date of the disease progression in the Overall Response form * The very last date by scanning all available dates in the database * The desired cut-off days The proportion of any time point will be determined by the Kaplan-Meier estimates.
Time frame: from first TACE to 12 months
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment. The subject continuously received follow-up but was not included in the per protocol group for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for PPF(Proportion Progression-Free) at 12 Months | EASL | 10 Percent of participants |
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for PPF(Proportion Progression-Free) at 12 Months | mRECIST | 8 Percent of participants |
Secondary
Kaplan-Meier Analyses the Percent of Participants for Time to Extrahepatic Spread
Kaplan-Meier analyses the percent of participants for Time to Extrahepatic Spread which the length of time from the treatment initiation to the development of extrahepatic spread of the disease via imaging assessment. The data items to be considered will include: * The date of the extrahepatic spread in the Overall Response form * The very last date by scanning all available dates in the database * The desired cut-off days
Time frame: At 12 month
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment. The subject continuously received follow-up but was not included in the per protocol group for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for Time to Extrahepatic Spread | 20 Percent of participants |
Secondary
Kaplan-Meier Analyses the Percent of Participants for Time to Progression (TTP) at 12 Months
Kaplan-Meier analyses the percent of participants for TTP which is defined as the length of time from the treatment initiation to either the date of the first disease progression occurred, as assessed by the investigators, or the date of the subject died due to any cause, whichever comes earlier. EASL and mRECIST response assessment of target lesion for HCC. TTP (also referred as time to treatment failure) will be measured by a few data items list below: * The date of the disease progression in the Overall Response form * The date of lost-to-follow due to: * Adverse events * Progressive disease/insufficient therapeutic response * Death * Failure to return * Refusing treatment/being unwilling to cooperate/withdrawing consent * The very last date by scanning all available dates in the database * The desired cut-off days
Time frame: At 12 months
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment. The subject continuously received follow-up but was not included in the per protocol group for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for Time to Progression (TTP) at 12 Months | EASL | 10 Percent of participants |
| Single -Arm | Kaplan-Meier Analyses the Percent of Participants for Time to Progression (TTP) at 12 Months | mRECIST | 8 Percent of participants |
Secondary
Number of Adverse Events Relate to Study Device in 12 Months Post Procedure
Number and documents of adverse events relate to study device in 12 months post procedure
Time frame: in 12 months
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment. The subject continuously received follow-up but was not included in the per protocol group for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single -Arm | Number of Adverse Events Relate to Study Device in 12 Months Post Procedure | SAEs of related with TANDEM Microspheres | 17 adverse events |
| Single -Arm | Number of Adverse Events Relate to Study Device in 12 Months Post Procedure | Non-serious AEs of related with TANDEM Microspheresrate | 301 adverse events |
Secondary
Number of Participants With Objective Tumor Response at 30-day
The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart.
Time frame: At 1month
Population: Measure Analysis Population Description: Measure Analysis Population Description: A total of 109 subjects were enrolled, among them one subject coded as 3733S010 was confirmed as cholangiocarcinoma after being enrolled and receiving initial treatment. The subject continuously received follow-up but was not included in the per protocol group for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single -Arm | Number of Participants With Objective Tumor Response at 30-day | EASL Response | 86 Participants |
| Single -Arm | Number of Participants With Objective Tumor Response at 30-day | mRECIST Response | 86 Participants |
Secondary
Number of Participants With Objective Tumor Response at 3 Months
The objective response rate measured by MRI used EASL (European Society for the Study of the Liver) and mRECIST (Improved criteria for evaluating the efficacy of solid tumors) , Overall Response (OR) = CR + PR. 1. Per Response Evaluation Criteria In Solid Tumors Criteria (mRECIST ) for target lesions : Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (EASL) for target lesions: Complete Response (CR), Disappearance of all known disease and no new lesions determined by two observations not less than 4 weeks apart; Partial Response (PR), At least 50% reduction in total tumor load of all measurable lesions determined by two observations not less than 4 weeks apart.
Time frame: At 3 months
Population: Total enrolled 109 subjects , 4 subjects were not completed 3 months primary endpoint follow up visit and were not included in the per protocol group for analysis. So overall Number of Participants Analyzed were 105.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single -Arm | Number of Participants With Objective Tumor Response at 3 Months | EASL Response | 84 Participants |
| Single -Arm | Number of Participants With Objective Tumor Response at 3 Months | mRECIST Response | 85 Participants |