search
Back to results

Hyperpolarized 13C Pyruvate MRI Scan in Predicting Tumor Aggressiveness in Patients With Renal Tumors

Primary Purpose

Benign Kidney Neoplasm, Kidney Neoplasm, Renal Cell Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized Carbon C 13 Pyruvate
Magnetic Resonance Imaging
Hyperpolarized 13C,15N2-urea
Sponsored by
Zhen Wang, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Benign Kidney Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Renal tumor measuring 1 cm and greater in diameter. To minimize any potential partial volume effects in this pilot study, we have limited the lower size range of the tumor to 1 cm. The investigators will include all renal tumor measuring 1 cm and greater in diameter in this first study to facilitate obtaining tumors of a range of histology and grade
  2. The subject is either scheduled to undergo partial or radical nephrectomy at University of California, San Francisco (UCSF), or is deemed clinically appropriate to undergo active surveillance for his/her renal tumor. The subject is able and willing to comply with study procedures and provide signed and dated informed consent
  3. The subject is willing to undergo standard of care abdominal MRI in connection with the study exam.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

  1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
  2. Patients unwilling or unable to undergo magnetic resonance (MR) imaging, including patients with contra-indications to MR imaging, such as cardiac pacemakers or non-compatible intracranial vascular clips.
  3. Any metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging of the abdomen.
  4. Prior focal therapy (i.e. ablation) for the renal tumor. In patients with tumor biopsy, imaging study will occur at least 4 weeks following any biopsy to avoid artifact from hemorrhage.
  5. Poorly controlled hypertension, with blood pressure at study entry >160/100. The addition of anti-hypertensives to control blood pressure is allowed for eligibility determination.
  6. Congestive heart failure or New York Heart Association (NYHA) status >= 2.

Sites / Locations

  • University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Diagnostic (HP 13C pyruvate with MRI)

Diagnostic (Combined (co-polarized) HP 13C pyruvate and 13C, 15N2 Urea with MRI)

Arm Description

Participants receive HP 13C pyruvate IV and then undergo 13C MRI scan 1-2 minutes post HP 13C pyruvate injection. Participants may receive an optional second HP 13C pyruvate injection and undergo 13C pyruvate MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI

Participants receive HP 13C pyruvate and 13C 15N2 urea IV and then undergo an MRI scan 1-2 minutes post injection. Participants may receive an optional second HP 13C pyruvate with 13C 15N2 urea injection and undergo a second MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI

Outcomes

Primary Outcome Measures

Comparison between HP 13C pyruvate-to-lactate conversion, as measured by peak lactate/pyruvate ratio with tumor histology and grade.
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. The investigators will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade renal cell carcinoma (RCC) vs. high grade RCCs based on the HP 13C pyruvate metabolic data
Comparison between HP 13C pyruvate-to-lactate conversion, as measured by the lactate /pyruvate area under curve (AUC) with tumor histology and grade.
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. We will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade RCCs vs. high grade RCCs based on the HP 13C pyruvate metabolic data;
Comparison between HP 13C pyruvate-to-lactate conversion, as measured by the apparent rate of constant metabolic flux of HP 13C-pyruvate to lactate (kPL), with tumor histology and grade.
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. The investigators will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade RCCs vs. high grade RCCs based on the HP 13C pyruvate metabolic data;

Secondary Outcome Measures

Estimate of intra-subject agreement for those with optional second scan
For participants who obtained an optional second HP 13 C pyruvate magnetic resonance imaging (MRI), intraclass correlation coefficient (ICC) will be used to estimate the intra-subject agreement. ICCs will be obtained from a one-way analysis of variance model based on 2 serial measurements per subject. The ICC ranges from 0 to 1. An ICC close to 1 indicates high similarity between values from the same group. An ICC close to zero means that values from the same group are not similar. The results will be presented with a 95% confidence interval.
Comparison of the HP 13C metabolism measures to change in tumor size
For participants who are in active surveillance for their renal tumors, MRI findings will be compared to tumor growth rate while on active surveillance. Correlations of HP 13C metabolism measures to change in tumor size on subsequent surveillance imaging studies will be performed using Pearson or rank correlation.
Incidence of treatment-related adverse events
Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology (Toxicity) Criteria for Adverse Events (CTCAE) version 4.0.

Full Information

First Posted
September 2, 2019
Last Updated
October 10, 2023
Sponsor
Zhen Wang, MD
Collaborators
American Cancer Society, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT04258462
Brief Title
Hyperpolarized 13C Pyruvate MRI Scan in Predicting Tumor Aggressiveness in Patients With Renal Tumors
Official Title
Hyperpolarized 13C Pyruvate Metabolic MRI to Predict Renal Tumor Aggressiveness
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 15, 2019 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zhen Wang, MD
Collaborators
American Cancer Society, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This feasibility study will evaluate how well hyperpolarized 13C pyruvate magnetic resonance imaging (MRI) scan works in predicting tumor aggressiveness in participants with renal tumors. Hyperpolarized 13C pyruvate is a non-radioactive substance with potential usage in the diagnostic imaging of tumors. Hyperpolarized 13C pyruvate MRI may help doctors determine non-invasively whether a kidney tumor is a benign tumor or cancer, and if cancer, how aggressive it is. This may help doctors and participants with renal tumors in the future to make better treatment decisions.
Detailed Description
PRIMARY OBJECTIVES: 1. To investigate the association between HP 13C pyruvate-to-lactate conversion (peak lactate/pyruvate ratio, lactate /pyruvate AUC (area under the curve), the apparent rate constant (kPL) and renal tumor histology (benign renal tumors versus RCCs) and grade (low vs high grade in cases of RCCs). SECONDARY OBJECTIVES: To determine the reproducibility of HP 13C pyruvate MRI in participants who undergo an optional second HP 13C pyruvate MRI. To investigate the association between HP 13 C pyruvate-to-lactate conversion and tumor growth rate in participants who are deemed clinically appropriate for active surveillance for their renal tumors. To determine the safety of HP 13C pyruvate in renal tumor participants. EXPLORATORY OBJECTIVES: To investigate the association between HP markers (peak lactate/pyruvate, lactate /pyruvate AUC, kPL) and tissue-based markers including Lactate Dehydrogenase A (LDHA) expression and lactate dehydrogenase (LDH) activity, and Monocarboxylate transporter 4 (MCT4) expression on tumor tissues from surgical specimen or from biopsy. To explore the correlation between HP 13C pyruvate-to-lactate conversion (peak lactate/pyruvate ratio, lactate/pyruvate AUC (area under the curve), the apparent rate constant kPL) and 13C urea tissue perfusion in the kidneys and renal tumors. OUTLINE: Participants receive HP 13C pyruvate intravenously (IV) or a combination of co-polarized 13C pyruvate and 13C, 15N2 Labeled urea (15N2) and then undergo MRI scan 1-2 minutes post injection Participants may receive an optional second HP 13C pyruvate intravenously (IV) or a combination of hyperpolarized 13C pyruvate and 13C, 15N2 urea injection and undergo 13C pyruvate MRI scan 15 to 30 minutes following completion of the first scan during the same imaging session, or the participant can return for a separate visit within 1-2 weeks from the first MRI to receive the optional second scan. After completion of study treatment, participants are followed up 30 minutes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Benign Kidney Neoplasm, Kidney Neoplasm, Renal Cell Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (HP 13C pyruvate with MRI)
Arm Type
Experimental
Arm Description
Participants receive HP 13C pyruvate IV and then undergo 13C MRI scan 1-2 minutes post HP 13C pyruvate injection. Participants may receive an optional second HP 13C pyruvate injection and undergo 13C pyruvate MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI
Arm Title
Diagnostic (Combined (co-polarized) HP 13C pyruvate and 13C, 15N2 Urea with MRI)
Arm Type
Experimental
Arm Description
Participants receive HP 13C pyruvate and 13C 15N2 urea IV and then undergo an MRI scan 1-2 minutes post injection. Participants may receive an optional second HP 13C pyruvate with 13C 15N2 urea injection and undergo a second MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized Carbon C 13 Pyruvate
Other Intervention Name(s)
Hyperpolarized 13C-Pyruvate, Hyperpolarized Pyruvate (13C)
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MRI, MRI Scan, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized 13C,15N2-urea
Other Intervention Name(s)
HP 13C, 15N2
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Comparison between HP 13C pyruvate-to-lactate conversion, as measured by peak lactate/pyruvate ratio with tumor histology and grade.
Description
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. The investigators will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade renal cell carcinoma (RCC) vs. high grade RCCs based on the HP 13C pyruvate metabolic data
Time Frame
Up to 12 months
Title
Comparison between HP 13C pyruvate-to-lactate conversion, as measured by the lactate /pyruvate area under curve (AUC) with tumor histology and grade.
Description
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. We will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade RCCs vs. high grade RCCs based on the HP 13C pyruvate metabolic data;
Time Frame
Up to 12 months
Title
Comparison between HP 13C pyruvate-to-lactate conversion, as measured by the apparent rate of constant metabolic flux of HP 13C-pyruvate to lactate (kPL), with tumor histology and grade.
Description
Descriptive statistics (mean, median, standard deviation, distribution, etc) of the metabolism measures will be calculated. The investigators will use a tree-based cross-validated Classification & Regression Trees (CART) model for predicting benign renal tumors vs. low grade RCCs vs. high grade RCCs based on the HP 13C pyruvate metabolic data;
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Estimate of intra-subject agreement for those with optional second scan
Description
For participants who obtained an optional second HP 13 C pyruvate magnetic resonance imaging (MRI), intraclass correlation coefficient (ICC) will be used to estimate the intra-subject agreement. ICCs will be obtained from a one-way analysis of variance model based on 2 serial measurements per subject. The ICC ranges from 0 to 1. An ICC close to 1 indicates high similarity between values from the same group. An ICC close to zero means that values from the same group are not similar. The results will be presented with a 95% confidence interval.
Time Frame
Up to 12 months
Title
Comparison of the HP 13C metabolism measures to change in tumor size
Description
For participants who are in active surveillance for their renal tumors, MRI findings will be compared to tumor growth rate while on active surveillance. Correlations of HP 13C metabolism measures to change in tumor size on subsequent surveillance imaging studies will be performed using Pearson or rank correlation.
Time Frame
Up to 12 months
Title
Incidence of treatment-related adverse events
Description
Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology (Toxicity) Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame
1 day, 30 minutes following hyperpolarized 13C pyruvate injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Renal tumor measuring 1 cm and greater in diameter. To minimize any potential partial volume effects in this pilot study, the investigators have limited the lower size range of the tumor to 1 cm. The investigators will include all renal tumor measuring 1 cm and greater in diameter in this first study to facilitate obtaining tumors of a range of histology and grade. The participant is being considered by the treating physician to have any of the following management options: partial or radical nephrectomy, ablation, or active surveillance for his/her renal tumor. The participant is able and willing to comply with study procedures and provide signed and dated informed consent. The participant is willing to undergo standard of care abdominal MRI in connection with the study exam. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: Participants who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent. Participants unwilling or unable to undergo magnetic resonance (MR) imaging, including patients with contra-indications to MR imaging, such as cardiac pacemakers or non-compatible intracranial vascular clips. Any metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging of the abdomen. Prior focal therapy (i.e. ablation) for the renal tumor. In participants with tumor biopsy, imaging study will occur at least 4 weeks following any biopsy to avoid artifact from hemorrhage. Poorly controlled hypertension, with blood pressure at study entry >160/100. The addition of anti-hypertensives to control blood pressure is allowed for eligibility determination. Congestive heart failure or New York Heart Association (NYHA) status >= 2.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhen Jane Wang, MD
Phone
415-476-3767
Email
Zhen.Wang@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Maya Aslam
Email
Maya.Aslam@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhen Jane Wang, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhen Jane Wang, MD
Phone
415-476-3767
Email
zhen.wang@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Maya Aslam
Phone
877-827-3222
Email
Maya.Aslam@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Zhen Jane Wang, MD
First Name & Middle Initial & Last Name & Degree
Peder Larson, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Hyperpolarized 13C Pyruvate MRI Scan in Predicting Tumor Aggressiveness in Patients With Renal Tumors

We'll reach out to this number within 24 hrs