Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Metastatic Renal Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT04831138
• Recruitment Status: Recruiting
• First Posted: April 5, 2021
• Last Update Posted: April 11, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Ananth Madhuranthakam, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

Magnetic Resonance Imaging (MRI) including Arterial Spin Labeling (ASL) will be performed before, during, and after the treatment, in a total of up to 6 MRI sessions until 7 months after the first session, or when progression is clinically indicated. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.

Clinically, metastatic renal cell carcinoma (RCC) patients are imaged every 2-3 months after the initiation of anti-angiogenic therapy, since morphological (i.e. size) changes are not anticipated earlier. However, our preliminary experience has shown functional changes including perfusion as early as 2-weeks after the initiation of the treatment. T0, T1, and T2 sessions will be performed for this proposal, while T3, T4, and T5 will be performed along with the clinical imaging sessions. All MR imaging sessions will be scheduled within ±1 or ±2 weeks of the target time period.

The research MR imaging may take approximately an additional 15 minutes per each imaging session, when done in conjunction with the clinical imaging. The T0, T1, and T2 research MR imaging sessions will be performed additionally for the purpose of this study, with each taking approximately one hour.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Procedure: MRI with ASL	Not Applicable

Detailed Description:

The incidence of kidney cancer has steadily increased over the past three to four decades and is among the 10 most frequently diagnosed cancers in the US. Approximately 63,990 new cases of kidney cancer are estimated in 2017 and the prognosis has been historically poor. The current 5-year survival rates are estimated at 74% overall, decreasing to 53% among patients with locally advanced diseases.

The most common form of kidney cancer, renal cell carcinoma (RCC), occurs in 90% of all kidney cancers. Among patients with localized RCC who are treated with nephrectomy, approximately one quarter have relapses in distant sites. Among patients with metastatic RCC, the 5-year survival rates are approximately 8%. With better understanding of the pathogenesis of the most common type of RCC, clear-cell renal cell carcinoma (ccRCC), newer treatment options with new agents are being developed to increase survival rates.

The high cost and potential risks associated with human trials for the newly developed experimental therapies have emphasized the need for sensitive monitoring of tumor response. Imaging approaches can play an important role in the evaluation and selection of potential new therapies with non-invasive longitudinal monitoring of treatment response. Currently, the radiological assessment of treatment outcomes predominantly relies on morphological (i.e. size) changes using the Response Evaluation Criteria in Solid Tumors (RECIST) and other similar scores. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede the eventual changes in tumor size. One such tumor property that has gained increased attention is angiogenesis, which has been shown to support tumor proliferation and infiltration. Increasing numbers of clinical trials have begun targeting tumor vascular supplies by directly inhibiting angiogenesis (e.g. antiangiogenic therapy). Such clinical trials and the eventual clinical use of these therapies would be greatly assisted by the availability of robust imaging indicators of angiogenesis (i.e. tissue perfusion).

Positron Emission Tomography (PET) using 15O-labeled water (15O-PET) is considered the gold standard for non-invasive measurement of tissue perfusion. However, the use of 15O-PET requires a cyclotron in close proximity to PET to produce short lived 15O-water (half life 2.4 min), limiting its applicability in clinical settings. Alternative imaging techniques include ultrasound using microbubbles, perfusion computed tomography (CT) using iodinated contrast agent and perfusion MRI using gadolinium based contrast agents. All of these techniques require exogenous agents, restricting their use in longitudinal monitoring of treatment response.

ASL-MRI has recently emerged as a quantitative imaging (QI) method to measure perfusion (or capillary blood flow) without the administration of exogenous contrast agents. ASL magnetically "labels" the highly permeable water in the blood as a tracer and measures their accumulation in the tissue of interest, without injecting any exogeneous contrast. Various versions of ASL have been validated in animals using microspheres, and in humans using 15O-PET in the brain. ASL also has a number of advantages compared to dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) based MR perfusion measurements. Specifically, ASL does not require exogenous agent alleviating the concerns of gadolinium accumulation or nephrogenic systemic fibrosis (NSF) in patients with impaired renal function and, unlike DCE/DSC, the contribution of vascular permeability to ASL measured perfusion is negligible enabling absolute perfusion quantification in physiological units.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Prospective Study to Evaluate Quantitative Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Metastatic Renal Cell Carcinoma
• Actual Study Start Date: March 24, 2021
• Estimated Primary Completion Date: March 24, 2026
• Estimated Study Completion Date: March 24, 2027

Arms and Interventions

Arm

Intervention/treatment

Experimental: RCC Patients; Patients with locally advanced or metastatic renal cell carcinoma

Procedure: MRI with ASL; T0 (Week 0): MRI with ASL will be performed either for research alone or along with patient's standard of care imaging session including contrast-enhancement. T1 (Day 7+-2): contrast-enhanced research MRI with ASL T2 (Day 14+-2): contrast-enhanced research MRI with ASL T3: MRI with ASL will be performed along with patient's standard of care imaging session. T4: MRI with ASL will be performed along with patient's standard of care imaging session. T5: MRI with ASL will be performed along with patient's standard of care imaging session.

Outcome Measures

Primary Outcome Measures :

1. Change in perfusion in the tumor [ Time Frame: Baseline to 7 and 14 days ]
   Will determine if changes in ASL measured tumor perfusion is associated with treatment response, measured as time to progression. One-sample correlation test will be used to determine the correlation between change in ASL measured tumor perfusion (baseline to 7+-2 days and 14+-2 days) and time to progression. The correlations will be measured and compared using Pearson's correlation coefficient along with 95% confidence interval.
2. Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
   Will determine if changes in ASL measured perfusion is associated with PFS. PFS will be correlated with baseline perfusion and post-treatment changes at 7-, and 14-days compared to baseline using univariable and multivariable Cox regression models. Will determine whether changes in ASL measured tumor perfusion as a continuous variable in the tumor from baseline to 7-, and 14-days after initiation of therapy is associated with PFS. The hazard ratio and its 95% confidence interval will be presented.

Secondary Outcome Measures :

1. ASL measured perfusion within enhancing tumor [ Time Frame: Baseline ]
   Will determine if ASL measured tumor perfusion at baseline is associated with treatment response, measured as time to progression. One-sample correlation test will be used to determine the correlation between baseline ASL measured tumor perfusion and time to progression. The correlations will be measured and compared using Pearson's correlation coefficient along with 95% confidence interval.
2. Overall Survival (OS) [ Time Frame: Up to 3 years ]
   Will determine if changes in ASL measured perfusion is associated with OS. OS will be correlated with baseline perfusion and post-treatment changes at 7- and 14-days compared to baseline using univariable and multivariable Cox regression models. Will determine whether changes in ASL measured tumor perfusion as a continuous variable within the tumor from baseline to 7-, and 14-days after initiation of therapy is associated with OS. The hazard ratio and its 95% confidence interval will be presented.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Patients with locally advanced or metastatic renal cell carcinoma.
• Patients scheduled to undergo anti-angiogenic treatment or immunotherapy
• Eastern Cooperative Oncology Group (ECOG) Status 0, 1 and 2.
• Women of child-bearing potential must agree to undergo a urine pregnancy screening per standard Radiology departmental protocol, in place to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Subjects may not be receiving any other anti-angiogenic agents, at the time of enrollment.
• Subjects must not be pregnant since pregnancy is a contraindication to administration of gadolinium-based contrast agents.
• Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices (e.g. pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign bodies.
• Known severe allergic reaction to Gadolinium-based contrast agents.
• Patients with sickle cell disease and patients with other hemolytic anemias (low red blood count in body).
• Patients with uncontrollable claustrophobia, severe lower back pain, and uncontrollable tremors, to the point that it would render them unable to tolerate an MRI study.

Contacts and Locations

Contacts

Contact: Kelli Key, PhD; 214-648-8152; Kelli.Key@UTSouthwestern.edu

Contact: Ananth Madhuranthakam, PhD; 214-648-7737; Ananth.Madhuranthakam@UTSouthwestern.edu

Locations

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Kelli Key, PhD 214-648-8152 Kelli.Key@UTSouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

More Information

• Responsible Party: Ananth Madhuranthakam, Director of MR Research and Associate Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT04831138
• Other Study ID Numbers: STU 032018-078
• First Posted: April 5, 2021
• Last Update Posted: April 11, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ananth Madhuranthakam, University of Texas Southwestern Medical Center:

magnetic resonance imaging; arterial spin labeling

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases