Back to resultsRadioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)
Primary Purpose
Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Computed Tomography
Hepatobiliary Iminodiacetic Acid Scan
Single Photon Emission Computed Tomography
Yttrium Y 90 Glass Microspheres
Yttrium-90 Microsphere Radioembolization
Sponsored by
About this trial
This is an interventional treatment trial for Stage III Hepatocellular Carcinoma AJCC v8
Eligibility Criteria
Inclusion Criteria:
- Patients over 18 years of age, of any race or sex, who have unresectable hepatocellular carcinoma of the liver, and who are able or have a fully able legal guardian to give informed consent, will be eligible. Patients must have an ECOG Performance Status score of </=2, with a life expectancy of >/=3 months, and must be non-pregnant with an acceptable contraception in premenopausal women. Patients must be >4 weeks since prior radiation or prior surgery and at least one month post chemotherapy.
- At least one lesion >/= 3.0 cm in shortest dimension
- AST or ALT <5 times ULN
- Bilirubin </= 2.0 mg/dL (unless segmental infusion is used)
- Negative pregnancy test in premenopausal women
Exclusion Criteria:
- Contraindications to angiography and selective visceral catheterization
- Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) to the lungs with a single injection, or greater than 50 Gy for multiple injections
- Evidence of any detectable Tc-99m MAA flow to the stomach or duodenum, after application of established angiographic techniques to stop or mitigate such flow (eg, placing catheter distal to gastric vessels)
- Significant extrahepatic disease representing an imminent life-threatening outcome
- Severe liver dysfunction or pulmonary insufficiency
- Active uncontrolled infection
- Significant underlying medical or psychiatric illness
- Pregnant
- Pre-existing diarrhea/illness, co-morbid disease or condition that would preclude safe delivery of TheraSphere® treatment and place the patient at undue risk
- Infiltrative tumors
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (personalized radioembolization, SPECT/CT HIDA)
Arm Description
Patients undergo yttrium-90 microsphere radioembolization with yttrium Y 90 glass microspheres using personalized dose measurements. Patients also undergo SPECT/CT HIDA scan before radioembolization and 2-4 months after radioembolization.
Outcomes
Primary Outcome Measures
Tumor objective response rate (ORR)
Assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The ORR of treated tumors will be determined. Will perform a cluster bootstrap in which patients (not tumors) are sampled with replacement. Will construct a 95% confidence interval using the 2.5% and 97.5% quantiles of the bootstrap sampling distribution.
Secondary Outcome Measures
Changes in liver function
Will analyze the correlation in changes in liver function to the mean absorbed dose to normal liver. The hepatobiliary iminodiacetic acid (HIDA) scan will be used to estimate the body-surface area corrected mebrofenin clearance rate in %-activity/sec/m^2 using published methodology. The change in liver function after radioembolization will be calculated and correlated to the radiation dose distribution to the normal liver. Will use Wilcoxon and two-sample t-tests to measure significance of association.
Changes in Common Terminology Criteria for Adverse Events (CTCAE) incidence
Will analyze the correlation in changes in CTCAE incidence to the mean absorbed dose to normal liver. Will create waterfall charts of CTCAE and mean absorbed normal liver in liver. Will use Wilcoxon and two-sample t-tests to measure significance of association and scatterplots and regression (linear or non-linear) to predict actual doses delivered from predicted tumor dose.
Accuracy of published tumor dose response prediction based on the yttrium-90 (Y90) tumor dose volume histograms
Lin's concordance correlation, t-test, and Bland-Altman analysis will be performed on pair-wise estimate of tumor doses. Develop tumor dose response curves using logistic regression and assess significance of parameters. Furthermore, we will compute the half-maximal dose (D50%), positive predictive value, negative predictive value and its 95% confidence interval from this prospective study. These values will be compared to those from the retrospective study for equivalence using the z-test.
Prediction of tumor doses macroaggregated albumin (MAA) scan with actual doses delivered (Y90 scan)
Lin's concordance correlation, t-test, and Bland-Altman analysis will be performed on pair-wise estimate of tumor doses. Will use scatterplots and regression (linear or non-linear) to predict actual doses delivered from predicted tumor dose. A correlation analysis of the predicted tumor doses from the MAA images with the actual tumor doses delivered from Y90 images will be performed. The linear-correlation coefficient will be computed. A Bland-Altman analysis will be performed to compute the bias and the 95% limits of agreement.
Development of tumor dose response model prediction based on MAA dose maps
Mean tumor doses based the planning 99mTc-MAA images will be computed using voxel dosimetry. A univariate logistic regression model will used to determine tumor dose metrics (D50%) that correlated with mRECIST-based tumor response at 3 and 6 months.
Development of a model correlating normal liver radiation dose to liver function using single-photon emission computed tomography computed tomography hepatobiliary iminodiacetic acid (SPECT CT HIDA) imaging
A regression analysis of the change in liver function from the pre- and post-procedural HIDA SPECT/CT scans (changes in %/min) as a function of the normal liver absorbed dose will be performed.
Full Information
NCT ID
NCT03896646
First Posted
March 28, 2019
Last Updated
September 26, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03896646
Brief Title
Radioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)
Official Title
Radioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 10, 2019 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial aims to improve hepatocellular carcinoma (HCC) tumor responses in patients undergoing Y90 radioembolization by using personalized dosimetry as part of treatment planning. Using standard calculations for Y90 doses may not be specific enough for individual patients given that there can be differences in how tumor cells and liver cells respond to radiation. Personalized dose plans may help improve treatment and outcomes in liver cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To achieve tumor objective response rates of 75% using voxel based dosimetry when the mean dose (Dmean) to tumor is targeted to be greater than 200 Gray (Gy).
SECONDARY OBJECTIVES:
I. Correlate changes in liver function and Common Terminology Criteria for Adverse Events (CTCAE) incidence to the mean absorbed dose to normal liver.
II. Prospectively validate the accuracy of our published tumor dose response prediction based on the yttrium Y 90 glass microspheres (yttrium-90 [Y90]) tumor dose volume histograms (DVHs).
III. Correlate predicted tumor doses macroaggregated albumin (MAA) scan with actual doses delivered (Y90 scan).
IV. Develop a tumor dose response model prediction based on the MAA dose maps. V. Develop a model correlating normal liver radiation dose to liver function using single-photon emission computed tomography/computed tomography hepatobiliary iminodiacetic acid (SPECT/CT HIDA) imaging.
VI. Develop a model correlating the relative tumor to normal liver enhancement on CT imaging and Cone beam CT imaging to the uptake on SPECT CT Tc99m MAA imaging (gold standard).
VII. Compare tumor and normal liver doses estimations from SPECT CT Bremsstrahlung imaging to positron emission tomography (PET) CT imaging.
OUTLINE:
Patients undergo yttrium-90 microsphere radioembolization with yttrium Y 90 glass microspheres using personalized dose measurements. Patients also undergo SPECT/CT HIDA scan before radioembolization and 2-4 months after radioembolization.
After completion of study treatment, patients are followed up at 3 and 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8, Stage IVB Hepatocellular Carcinoma AJCC v8, Unresectable Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (personalized radioembolization, SPECT/CT HIDA)
Arm Type
Experimental
Arm Description
Patients undergo yttrium-90 microsphere radioembolization with yttrium Y 90 glass microspheres using personalized dose measurements. Patients also undergo SPECT/CT HIDA scan before radioembolization and 2-4 months after radioembolization.
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography
Intervention Description
Undergo SPECT/CT HIDA scan
Intervention Type
Other
Intervention Name(s)
Hepatobiliary Iminodiacetic Acid Scan
Other Intervention Name(s)
HIDA Scan
Intervention Description
Undergo SPECT/CT HIDA scan
Intervention Type
Procedure
Intervention Name(s)
Single Photon Emission Computed Tomography
Other Intervention Name(s)
Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, single-photon emission computed tomography, SPECT, SPECT imaging, SPECT SCAN, SPET, tomography, emission computed, single photon, Tomography, Emission-Computed, Single-Photon
Intervention Description
Undergo SPECT/CT HIDA scan
Intervention Type
Radiation
Intervention Name(s)
Yttrium Y 90 Glass Microspheres
Other Intervention Name(s)
TheraSphere
Intervention Description
Undergo radioembolization with yttrium Y 90 glass microspheres
Intervention Type
Procedure
Intervention Name(s)
Yttrium-90 Microsphere Radioembolization
Other Intervention Name(s)
Yttrium Y 90 Microsphere Therapy, Yttrium-90 Radioembolization
Intervention Description
Undergo yttrium-90 microsphere radioembolization
Primary Outcome Measure Information:
Title
Tumor objective response rate (ORR)
Description
Assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The ORR of treated tumors will be determined. Will perform a cluster bootstrap in which patients (not tumors) are sampled with replacement. Will construct a 95% confidence interval using the 2.5% and 97.5% quantiles of the bootstrap sampling distribution.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Changes in liver function
Description
Will analyze the correlation in changes in liver function to the mean absorbed dose to normal liver. The hepatobiliary iminodiacetic acid (HIDA) scan will be used to estimate the body-surface area corrected mebrofenin clearance rate in %-activity/sec/m^2 using published methodology. The change in liver function after radioembolization will be calculated and correlated to the radiation dose distribution to the normal liver. Will use Wilcoxon and two-sample t-tests to measure significance of association.
Time Frame
Up to 6 months
Title
Changes in Common Terminology Criteria for Adverse Events (CTCAE) incidence
Description
Will analyze the correlation in changes in CTCAE incidence to the mean absorbed dose to normal liver. Will create waterfall charts of CTCAE and mean absorbed normal liver in liver. Will use Wilcoxon and two-sample t-tests to measure significance of association and scatterplots and regression (linear or non-linear) to predict actual doses delivered from predicted tumor dose.
Time Frame
Up to 6 months
Title
Accuracy of published tumor dose response prediction based on the yttrium-90 (Y90) tumor dose volume histograms
Description
Lin's concordance correlation, t-test, and Bland-Altman analysis will be performed on pair-wise estimate of tumor doses. Develop tumor dose response curves using logistic regression and assess significance of parameters. Furthermore, we will compute the half-maximal dose (D50%), positive predictive value, negative predictive value and its 95% confidence interval from this prospective study. These values will be compared to those from the retrospective study for equivalence using the z-test.
Time Frame
Up to 6 months
Title
Prediction of tumor doses macroaggregated albumin (MAA) scan with actual doses delivered (Y90 scan)
Description
Lin's concordance correlation, t-test, and Bland-Altman analysis will be performed on pair-wise estimate of tumor doses. Will use scatterplots and regression (linear or non-linear) to predict actual doses delivered from predicted tumor dose. A correlation analysis of the predicted tumor doses from the MAA images with the actual tumor doses delivered from Y90 images will be performed. The linear-correlation coefficient will be computed. A Bland-Altman analysis will be performed to compute the bias and the 95% limits of agreement.
Time Frame
Up to 6 months
Title
Development of tumor dose response model prediction based on MAA dose maps
Description
Mean tumor doses based the planning 99mTc-MAA images will be computed using voxel dosimetry. A univariate logistic regression model will used to determine tumor dose metrics (D50%) that correlated with mRECIST-based tumor response at 3 and 6 months.
Time Frame
Up to 6 months
Title
Development of a model correlating normal liver radiation dose to liver function using single-photon emission computed tomography computed tomography hepatobiliary iminodiacetic acid (SPECT CT HIDA) imaging
Description
A regression analysis of the change in liver function from the pre- and post-procedural HIDA SPECT/CT scans (changes in %/min) as a function of the normal liver absorbed dose will be performed.
Time Frame
Up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients over 18 years of age, of any race or sex, who have unresectable hepatocellular carcinoma of the liver, and who are able or have a fully able legal guardian to give informed consent, will be eligible. Patients must have an ECOG Performance Status score of </=2, with a life expectancy of >/=3 months, and must be non-pregnant with an acceptable contraception in premenopausal women. Patients must be >4 weeks since prior radiation or prior surgery and at least one month post chemotherapy.
At least one lesion >/= 3.0 cm in shortest dimension
AST or ALT <5 times ULN
Bilirubin </= 2.0 mg/dL (unless segmental infusion is used)
Negative pregnancy test in premenopausal women
Exclusion Criteria:
Contraindications to angiography and selective visceral catheterization
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) to the lungs with a single injection, or greater than 50 Gy for multiple injections
Evidence of any detectable Tc-99m MAA flow to the stomach or duodenum, after application of established angiographic techniques to stop or mitigate such flow (eg, placing catheter distal to gastric vessels)
Significant extrahepatic disease representing an imminent life-threatening outcome
Severe liver dysfunction or pulmonary insufficiency
Active uncontrolled infection
Significant underlying medical or psychiatric illness
Pregnant
Pre-existing diarrhea/illness, co-morbid disease or condition that would preclude safe delivery of TheraSphere® treatment and place the patient at undue risk
Infiltrative tumors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armeen Mahvash
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website
Learn more about this trial
Radioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)
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