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unable to recruit. terminated due to futility
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The proposed study is a single site, prospective, randomized pilot study to assess the feasibility of recruitment of patients into a trial evaluating the efficacy and tolerability of selective transarterial Y90 radioembolization (radiation segmentectomy) versus stereotactic body radiation therapy (SBRT) for solitary early stage (≤ 3cm) hepatocellular carcinoma (HCC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Yttrium-90 Radiation Segmentectomy | Active Comparator |
| |
| Stereotactic Body Radiation Therapy | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Yttrium-90 Radiation Segmentectomy | Radiation | This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded. |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of Recruitment (Recruitment Rate) | Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Any Toxicities | the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 16 months for the first subject and 4 months for the second |
| Mean Change in Hepatobiliary Function |
Not provided
Inclusion Criteria:
Ability to provide written informed consent and HIPAA authorization
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged ≥ 18 years at time of informed consent
Solitary HCC (≤3 cm) diagnosed by imaging (LI-RADS 4-5) or histology
Childs-Pugh score ≤ 7
ECOG performance status 0-1
Tumor location/characteristics eligible for either SBRT or Y90 therapy as deemed by local tumor board
Adequate organ function defined as:
Exclusion Criteria:
Any prior locoregional therapy to the target tumor
Any prior radiation therapy to the liver
Pregnancy or lactation: Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
i. Has undergone a hysterectomy or bilateral oophorectomy; or ii. Has been naturally amenorrheic for at least 24 consecutive months
Known severe allergic reaction (anaphylaxis) to iodinated contrast
Coagulopathy (platelets < 50 K/mm3 and/or INR > 2) not correctable by transfusion
Macrovascular invasion or extrahepatic HCC
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Indianapolis | Indiana | 46202 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Yttrium-90 Radiation Segmentectomy | Yttrium-90 Radiation Segmentectomy: This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded. |
| FG001 | Stereotactic Body Radiation Therapy | Stereotactic Body Radiation Therapy: SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Yttrium-90 Radiation Segmentectomy | Yttrium-90 Radiation Segmentectomy: This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Feasibility of Recruitment (Recruitment Rate) | Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate. | This group consists of all patients who fit inclusion/exclusion criteria and were approached for enrollment in the study | Posted | Count of Participants | Participants | 24 months |
|
|
adverse event data was planned to be collected for up to 24 months. however, total AE data only collected for 15 months from enrollment (at the longest) secondary to pt drop out.
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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 | Yttrium-90 Radiation Segmentectomy | Yttrium-90 Radiation Segmentectomy: This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| fatigue | General disorders | Systematic Assessment | grade 1 fatigue |
This study was originally planned as a pilot in hopes of being able to demonstrate feasibility of recruitment into a trail where one arm involved invasive therapy and one non-invasive. Unfortunately, the trial opened very shortly after the beginning of the pandemic in 2020 and overall recruitment/resources for research were hindered. after close to 18 months with little enrollment the funding entity and research team agreed it should just be terminated early for futility.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul Haste | Indiana University School of Medicine | 317-944-5005 | phaste@iu.edu |
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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 | Dec 15, 2021 | Apr 6, 2023 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
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Radiologist assessing response will be blinded to the treatment type
|
| Stereotactic Body Radiation Therapy | Radiation | SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week. |
|
the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). |
| 16 months for the first subject and 4 months for the second |
| Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G). scale goes from 0-108 with a higher score being better. | 6 months |
| Mean Change in Comprehensive Score for Financial Toxicity | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST). scale is from 0-44 with higher being bettter | 6 months |
| Disease-free Survival (DFS) Rates of RS and SBRT | the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 16 months for the first subject and 4 months for the second |
| Time-to-secondary Treatment (TTST) Between RS and SBRT | time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment. | 16 months for the first subject and 4 months for the second |
| Objective Response Rate | the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments. | 6 months |
| BG001 | Stereotactic Body Radiation Therapy | Stereotactic Body Radiation Therapy: SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Participants |
|
|
| Secondary | Proportion of Patients With Any Toxicities | the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | No data were collected for this outcome measure because 0 participants remained enrolled in this time frame | Posted | 16 months for the first subject and 4 months for the second |
|
|
| Secondary | Mean Change in Hepatobiliary Function | the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | 1 pt in y90 arm had 3 month scan to compare to baseline. no other scans | Posted | Number | percentage of liver function decrease | 16 months for the first subject and 4 months for the second |
|
|
|
| Secondary | Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G). scale goes from 0-108 with a higher score being better. | for single Y90 pt data was collected. Data not collected for SBRT pt. | Posted | Number | score on a scale | 6 months |
|
|
|
| Secondary | Mean Change in Comprehensive Score for Financial Toxicity | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST). scale is from 0-44 with higher being bettter | data collected for single y90 pt. data not collected for SBRT pt | Posted | Number | score on a scale | 6 months |
|
|
|
| Secondary | Disease-free Survival (DFS) Rates of RS and SBRT | the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). | No data were collected for this outcome measure because 0 participants remained enrolled in this time frame | Posted | 16 months for the first subject and 4 months for the second |
|
|
| Secondary | Time-to-secondary Treatment (TTST) Between RS and SBRT | time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment. | No data were collected for this outcome measure because 0 participants remained enrolled in this time frame | Posted | 16 months for the first subject and 4 months for the second |
|
|
| Secondary | Objective Response Rate | the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments. | No data were collected for this outcome measure because 0 participants in the SBRT arm remained enrolled in this time frame and 6 month imaging was unavailable for the pt in the y90 arm | Posted | 6 months |
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Stereotactic Body Radiation Therapy | Stereotactic Body Radiation Therapy: SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week. | 0 | 1 | 0 | 1 | 1 | 1 |
| nausea | Gastrointestinal disorders | Systematic Assessment | grade 1 |
|
| right leg bruise | Surgical and medical procedures | Systematic Assessment | grade 1 bruise |
|
| elevated vitamin D | General disorders | Systematic Assessment | grade 1 |
|
| elevated AFP | Hepatobiliary disorders | Systematic Assessment | grade 1 |
|
| elevated AST | Hepatobiliary disorders | Systematic Assessment | grade 1 |
|
| low serum carbon dioxide | General disorders | Systematic Assessment | grade 1 |
|
| high anion gap | General disorders | Systematic Assessment | grade 1 |
|
| decreased lymphocyte count | Blood and lymphatic system disorders | Systematic Assessment | grade 1 |
|
| decreased platelet count decreased | Blood and lymphatic system disorders | Systematic Assessment | grade 1 |
|
| glucose intolerance | General disorders | Systematic Assessment | grade 1 |
|
| ALT increased | General disorders | Systematic Assessment | grade 1 |
|
| perirectal abscess | General disorders | Systematic Assessment | grade 2 |
|
| increased size of left renal mass | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | grade 1 |
|
| low sodium | General disorders | Systematic Assessment | grade 1 |
|
| decreased lymphocyte count | Blood and lymphatic system disorders | Systematic Assessment | grade 2 |
|
| decreased lymphocyte count | Blood and lymphatic system disorders | Systematic Assessment | grade 3 |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment | grade 2 |
|
| low creatinine | General disorders | Systematic Assessment | grade 1 |
|
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| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D013514 |
| Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| Title | Measurements |
|---|---|
|
| 6 month |
|
| Title | Measurements |
|---|
|
| 6 month |
|