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| Name | Class |
|---|---|
| Varian Medical Systems | INDUSTRY |
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This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a "bridge" to orthotopic liver transplantation.
For patients with hepatocellular carcinoma (HCC) who are waiting for a liver transplant, local treatment of their disease has become the standard of care in an effort to decrease dropout rates and as a means of reducing tumor recurrence after transplantation. However, the best modality for patients undergoing treatment as a bridge to transplantation is unclear. This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a "bridge" to orthotopic liver transplantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Other | Stereotactic Body Radiation Therapy (SBRT) |
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| Arm B | Other | Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) | Radiation | SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days. |
| Measure | Description | Time Frame |
|---|---|---|
| Freedom From Progression Over Time | Time from SBRT and TACE intervention to progression was tracked for subject receiving protocol intervention. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion. | 3, 6 and 12 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE | Grade 3 or greater toxicity with treatment-related adverse events was tracked at protocol specific time points. Grading of events was according to CTCAE. | At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment |
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Inclusion Criteria
Hepatocellular carcinoma is defined as having at least one of the following:
Biopsy proven hepatocellular carcinoma (HCC); or A discrete hepatic tumor(s) as defined by the Barcelona (29) criteria for cirrhotic patients, >2cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI.
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Francis W Nugent, MD | Lahey Hospital & Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lahey Hospital & Medical Center | Burlington | Massachusetts | 01805 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A | Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days. |
| FG001 | Arm B |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 18, 2017 |
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| Trans-Arterial Chemoembolization (TACE) | Procedure | First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. |
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| Doxorubin | Drug | This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin. |
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| Number of Participants Who Require Further Interventions Prior to Liver Transplant | Each patient on each arm was followed to see how if further treatment interventions were needed prior to liver transplant. This outcome summarizes the number of participants who needed further treatment. | 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment |
| Pathologic Response of Treated Lesion(s) | Pathologic complete response was recorded for patients in both arms after completion of liver transplant. Explanted liver was reviewed by the pathologist to determine if residual tumor was identified. | At time of liver transplant |
| Radiologic Response of Treat Lesion(s) | Number of patients with a radiographical response to treatment.The status of each treated tumor/target lesion was assessed by MRI or CT scan and classified as progression if there was tumor growth (excluding growth due to biloma or abscess formation), residual or new enhancement of the ablated tumor (excluding benign peri-ablational enhancement), or contiguous viable tumor as determined by mRECIST Criteria. | Baseline, 3 months post-treatment, 6 months post-treatment, every 3 months thereafter until 2 years post treatment |
| Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey | Quality of life was assessed with Short Form 36 Health Survey (SF-36v2®) and Pain Impact Questionnaire (PIQ-6TM) Health Survey. Data was stored and scored with Pro CoRE 2.0 Smart Measurement® System. Scores were analyzed at three time points, baseline-before the first treatment, acute response-2 weeks post the first treatment, and long term response - 6 months after the first treatment. The PIQ-6 Pain Impact Questionnaire measures how a subject's pain affects every day activities. The SF-36v2 Health Survey measures functional health and well-being from the subject's point of view. The survey's scores range from 0-100, with 0 having the most disability and a score of 100 being equivalent to no disability. | Baseline, 2 weeks post-treatment, 6 months post-treatment |
Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin. |
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| NOT COMPLETED |
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60 pts were consented, 12 pts failed to undergo treatment. Among the 12 not treated, 6 pts were screen failures. Additionally, 4 pts were randomized but declared ineligible before treatment. Two more pts underwent treatment and were excluded from analysis: 1 pt treated on the SBRT arm was misdiagnosed (large cell lymphoma) and 1 pt on the TACE arm was lost to follow up.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A | Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days. |
| BG001 | Arm B | Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Freedom From Progression Over Time | Time from SBRT and TACE intervention to progression was tracked for subject receiving protocol intervention. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion. | Posted | Number | 95% Confidence Interval | percentage of patients with progression | 3, 6 and 12 Months |
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| Secondary | Toxicity To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE | Grade 3 or greater toxicity with treatment-related adverse events was tracked at protocol specific time points. Grading of events was according to CTCAE. | Subjects in both arms were observed for adverse events at protocol specific time points. | Posted | Count of Participants | Participants | At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment |
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| Secondary | Number of Participants Who Require Further Interventions Prior to Liver Transplant | Each patient on each arm was followed to see how if further treatment interventions were needed prior to liver transplant. This outcome summarizes the number of participants who needed further treatment. | Posted | Number | participants | 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment |
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| Secondary | Pathologic Response of Treated Lesion(s) | Pathologic complete response was recorded for patients in both arms after completion of liver transplant. Explanted liver was reviewed by the pathologist to determine if residual tumor was identified. | Patients undergoing liver transplant were reviewed for complete pathologic response. | Posted | Count of Participants | Participants | At time of liver transplant |
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| Secondary | Radiologic Response of Treat Lesion(s) | Number of patients with a radiographical response to treatment.The status of each treated tumor/target lesion was assessed by MRI or CT scan and classified as progression if there was tumor growth (excluding growth due to biloma or abscess formation), residual or new enhancement of the ablated tumor (excluding benign peri-ablational enhancement), or contiguous viable tumor as determined by mRECIST Criteria. | Posted | Count of Participants | Participants | Baseline, 3 months post-treatment, 6 months post-treatment, every 3 months thereafter until 2 years post treatment |
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| Secondary | Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey | Quality of life was assessed with Short Form 36 Health Survey (SF-36v2®) and Pain Impact Questionnaire (PIQ-6TM) Health Survey. Data was stored and scored with Pro CoRE 2.0 Smart Measurement® System. Scores were analyzed at three time points, baseline-before the first treatment, acute response-2 weeks post the first treatment, and long term response - 6 months after the first treatment. The PIQ-6 Pain Impact Questionnaire measures how a subject's pain affects every day activities. The SF-36v2 Health Survey measures functional health and well-being from the subject's point of view. The survey's scores range from 0-100, with 0 having the most disability and a score of 100 being equivalent to no disability. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 2 weeks post-treatment, 6 months post-treatment |
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Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A | Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days. | 0 | 19 | 0 | 19 | 7 | 19 |
| EG001 | Arm B | Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin. | 1 | 29 | 2 | 29 | 5 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis and GI Bleed | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
| |
| biliary infection | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| RILD with refractory ascities | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
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| fatigue | General disorders | CTCAE (Unspecified) | Systematic Assessment |
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| thrombocytopenia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
| |
| hepatic pain | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
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| bacterial peritonitis | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
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| WBC decreased | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
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| hypertension | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment |
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| anemia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
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| lymphopenia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
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| portal vein thrombosis | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
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| hepatic infarct | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
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| esophageal varices hemorrhage | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
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One primary limitation was the small, single institution, randomized phase II design. Given the small overall numbers, no definitive judgements can be made.
Another potential weakness of the trial was the selection of our primary endpoint. Our primary endpoint was time to residual or progressive cancer in the previously treated lesion(s).
A third limitation of this trial was incomplete compliance with QOL questionnaires. Lastly, our QOL measures were performed over a long interval.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julia Roache | Lahey Hospital & Medical Center | 781-744-3055 | julia.roache@lahey.org |
| Aug 7, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| D011878 | Radiotherapy |
| D016461 | Chemoembolization, Therapeutic |
| D004317 | Doxorubicin |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D004621 | Embolization, Therapeutic |
| D006489 | Hemostatic Techniques |
| D060205 | Therapeutic Occlusion |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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