Intrahepatic Cholangiocarcinoma
Conditions
Brief summary
This phase II trial tests whether contrast-enhanced ultrasound can predict the response of bile duct cancer to targeted radiotherapy (radioembolization treatment). Contrast-enhanced ultrasound uses gas microbubbles that may provide enhancement on ultrasound. It is also possible to pop these microbubbles using ultrasound imaging. Tumors that experience popping of these microbubbles may be easier to kill with radiotherapies. Therefore, this trial may also help doctors see if ultrasound-triggered microbubble popping can improve bile duct cancer response to radiotherapy. Another purpose of this trial is to test if the pressure inside the tumor estimated through ultrasound can be used to predict the tumor response to radiotherapy.
Detailed description
PRIMARY OBJECTIVE: I. To determine the ability of quantitative volumetric contrast-enhanced ultrasound (CEUS) to predict non-hepatocellular carcinoma (HCC) tumor response to transarterial radioembolization (TARE) prior to therapy. SECONDARY OBJECTIVES: I. To characterize the safety and preliminary efficacy of using localized ultrasound contrast agent (UCA) inertial cavitation to improve ICC response to radioembolization. II. To determine if CEUS estimated tumor perfusion and residual vascularity 7-14 days post treatment can predict ICC response to radioembolization. III. To evaluate tumoral response using the patient's 1 month magnetic resonance imaging (MRI) (obtained clinically) and determine the accuracy of MR or computed tomography (CT) tumor evaluation at this earlier time point. EXPLORATORY OBJECTIVE: I. To examine the utility of subharmonic aided pressure estimation (SHAPE) to noninvasively monitor tumoral interstitial fluid pressure (IFP) and provide an early biomarker of radiotherapy response. OUTLINE: Patients receive perflutren protein-type A microspheres intravenously (IV) over 10 minutes and undergo ultrasound at 1 month before TARE, 1-4 hours, 1 week, and 2 weeks post-TARE. After completion of study, patients are followed for 1 year.
Interventions
Given IV
PROCEDUREContrast-Enhanced Ultrasound
Undergo CEUS
Sponsors
National Cancer Institute (NCI)
Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be scheduled for sub-lobar radioembolization therapy of a previously untreated intrahepatic cholangiocarcinoma greater than 1 cm but small enough to be fully visualized in the ultrasound three-dimensional (3D) volume (approximately 6 cm maximum diameter, but depth dependent) * Be at least 18 years of age * Be medically stable * If a female of child-bearing age, have a negative pregnancy test prior to each ultrasound exam * Have signed Informed Consent to participate in the study
Exclusion criteria
* Females who are pregnant or nursing * Patients with recent cerebral hemorrhage * Patients with known sensitivities to albumin, blood, or blood products * Patients with known hypersensitivity to perflutren * Patients with known congenital heart defects * Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli * Patients with bilirubin levels \> 2 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tumor Complete Response (CR) | assessed at 3 to 6 months post-TARE | Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met. |
| Number of Participants With Tumor Partial Response (PR) | assessed at 3 to 6 months post-TARE | Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met. |
| Number of Participants With Stable Disease | assessed at 3 to 6 months post-TARE | Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met. |
| Number of Participants With Progressive Disease | assessed at 3 to 6 months post-TARE | Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnostic (perflutren protein-type A microspheres, CEUS) Patients receive perflutren protein-type A microspheres IV over 10 minutes and undergo ultrasound at 1 month before TARE, 1-4 hours, 1 week, and 2 weeks post-TARE.
Perflutren Protein-Type A Microspheres: Given IV
Contrast-Enhanced Ultrasound: Undergo CEUS | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | imaging not obtained for primary outcome assessment | 1 |
| Overall Study | Treatment cancelled prior to radioembolization | 1 |
Baseline characteristics
| Characteristic | Diagnostic (perflutren protein-type A microspheres, CEUS) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Number of Participants With Progressive Disease
Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Time frame: assessed at 3 to 6 months post-TARE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnostic (perflutren protein-type A microspheres, CEUS) | Number of Participants With Progressive Disease | 0 Participants |
Primary
Number of Participants With Stable Disease
Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Time frame: assessed at 3 to 6 months post-TARE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnostic (perflutren protein-type A microspheres, CEUS) | Number of Participants With Stable Disease | 4 Participants |
Primary
Number of Participants With Tumor Complete Response (CR)
Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Time frame: assessed at 3 to 6 months post-TARE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnostic (perflutren protein-type A microspheres, CEUS) | Number of Participants With Tumor Complete Response (CR) | 7 Participants |
Primary
Number of Participants With Tumor Partial Response (PR)
Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Time frame: assessed at 3 to 6 months post-TARE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnostic (perflutren protein-type A microspheres, CEUS) | Number of Participants With Tumor Partial Response (PR) | 3 Participants |