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Radioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)

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ClinicalTrials.gov Identifier: NCT03896646
Recruitment Status : Not yet recruiting
First Posted : April 1, 2019
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Procedure: Computed Tomography Other: Hepatobiliary Iminodiacetic Acid Scan Procedure: Single Photon Emission Computed Tomography Radiation: Yttrium Y 90 Glass Microspheres Procedure: Yttrium-90 Microsphere Radioembolization Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Radioembolization for HCC Patients With Personalized Yttrium-90 Dosimetry for Curative Intent (RAPY90D)
Estimated Study Start Date : August 31, 2019
Estimated Primary Completion Date : January 30, 2020
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Yttrium

Arm Intervention/treatment
Experimental: Treatment (personalized radioembolization, SPECT/CT HIDA)
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.
Procedure: Computed Tomography
Undergo SPECT/CT HIDA scan
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • computerized tomography
  • CT
  • CT SCAN
  • tomography

Other: Hepatobiliary Iminodiacetic Acid Scan
Undergo SPECT/CT HIDA scan
Other Name: HIDA Scan

Procedure: Single Photon Emission Computed Tomography
Undergo SPECT/CT HIDA scan
Other Names:
  • 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

Radiation: Yttrium Y 90 Glass Microspheres
Undergo radioembolization with yttrium Y 90 glass microspheres
Other Name: TheraSphere

Procedure: Yttrium-90 Microsphere Radioembolization
Undergo yttrium-90 microsphere radioembolization
Other Names:
  • Yttrium Y 90 Microsphere Therapy
  • Yttrium-90 Radioembolization




Primary Outcome Measures :
  1. Tumor objective response rate (ORR) [ Time Frame: Up to 6 months ]
    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 :
  1. Changes in liver function [ Time Frame: Up to 6 months ]
    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.

  2. Changes in Common Terminology Criteria for Adverse Events (CTCAE) incidence [ Time Frame: Up to 6 months ]
    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.

  3. Accuracy of published tumor dose response prediction based on the yttrium-90 (Y90) tumor dose volume histograms [ Time Frame: Up to 6 months ]
    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.

  4. Prediction of tumor doses macroaggregated albumin (MAA) scan with actual doses delivered (Y90 scan) [ Time Frame: Up to 6 months ]
    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.

  5. Development of tumor dose response model prediction based on MAA dose maps [ Time Frame: Up to 6 months ]
    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.

  6. 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 [ Time Frame: Up to 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients over 18 years of age, of any race or sex
  • Patients who have unresectable hepatocellular carcinoma of the liver.
  • Patients who are able or have a fully able legal guardian to give informed consent.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2.
  • A life expectancy of >= 3 months.
  • 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.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 5 times upper limit of normal (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 technetium Tc-99m albumin aggregated (Tc-99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop or mitigate such flow (e.g., 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03896646


Contacts
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Contact: Armeen Mahvash 713-563-7340 armeen.mahvash@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Armeen Mahvash    713-563-7340      
Principal Investigator: Armeen Mahvash         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Armeen Mahvash M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03896646     History of Changes
Other Study ID Numbers: 2018-1008
NCI-2019-01586 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-1008 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Iminodiacetic acid
Molecular Mechanisms of Pharmacological Action
Chelating Agents
Sequestering Agents