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

• ClinicalTrials.gov Identifier: NCT04258462
• Recruitment Status: Recruiting
• First Posted: February 6, 2020
• Last Update Posted: November 25, 2020
• Sponsor: Zhen Wang, MD
• Collaborator: American Cancer Society, Inc.
• Information provided by (Responsible Party): Zhen Wang, MD, University of California, San Francisco

Tracking Information

• First Submitted Date: September 2, 2019
• First Posted Date: February 6, 2020
• Last Update Posted Date: November 25, 2020
• Actual Study Start Date: January 1, 2019
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2020)

• Comparison between HP 13C pyruvate-to-lactate conversion, as measured by peak lactate/pyruvate ratio with tumor histology and grade. [ Time Frame: Up to 12 months ]
  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 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. [ Time Frame: Up to 12 months ]
  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. [ Time Frame: Up to 12 months ]
  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;

Original Primary Outcome Measures (submitted: February 4, 2020)

• Comparison between hyperpolarized (HP) 13C pyruvate-to-lactate conversion, as measured by lactate/pyruvate ratio, with tumor histology and grade. [ Time Frame: Up to 12 months ]
  Will be tested using A Kruskal-Wallis one-way analysis of variance (ANOVA) model.
• Comparison between HP 13C pyruvate-to-lactate conversion, as measured by the apparent rate constant kPL, with tumor histology and grade. [ Time Frame: Up to 12 months ]
  Will be tested using A Kruskal-Wallis one-way analysis of variance (ANOVA) model.

Current Secondary Outcome Measures (submitted: November 22, 2020)

• Estimate of intra-subject agreement for those with optional second scan [ Time Frame: Up to 12 months ]
  For patients 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 magnetic resonance (MR) peak lactate/pyruvate with Lactate dehydrogenase-A (LDHA) expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR peak lactate/pyruvate with Lactate dehydrogenase (LDH) activity [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR peak lactate/pyruvate with MCT4 expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR lactate /pyruvate area under the curve (AUC) with LDHA expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR lactate /pyruvate AUC with LDH activity [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR lactate /pyruvate AUC with MCT4 expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR kPL with LDHA expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR kPL with LDH activity [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Comparison of the HP MR kPL with MCT4 expression [ Time Frame: Up to 12 months ]
  When both the HP biomarker and molecular biomarker are continuous variables, Spearman's rank correlation coefficient will be used to investigate a possible correlation between them. If the outcome is categorical (e.g. immunohistochemistry score 0-1+ vs 2-3+), the HP biomarker distributions will be compared for the two categories using the Mann-Whitney test.
• Incidence of treatment-related adverse events [ Time Frame: 1 day, 30 minutes following hyperpolarized 13C pyruvate injection ]
  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.

Original Secondary Outcome Measures (submitted: February 4, 2020)

• Comparison of HP markers, as measured by lactate/pyruvate ratio, with tissue-based markers including Lactate dehydrogenase-A (LDHA) expression [ Time Frame: Up to 12 months ]
  Will be tested using A Kruskal-Wallis one-way analysis of variance (ANOVA) model.
• Comparison of HP markers, as measured by apparent rate constant kPL, with tissue-based markers including Lactate dehydrogenase-A (LDHA) expression [ Time Frame: Up to 12 months ]
  Will be tested using A Kruskal-Wallis one-way analysis of variance (ANOVA) model.
• Incidence of treatment-related adverse events [ Time Frame: 1 day, 30 minutes following hyperpolarized 13C pyruvate injection ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hyperpolarized 13C Pyruvate MRI Scan in Predicting Tumor Aggressiveness in Patients With Localized Renal Tumor
• Official Title: Hyperpolarized 13C Pyruvate Metabolic MRI to Predict Renal Tumor Aggressiveness
• Brief Summary: This feasibility study will evaluate how well hyperpolarized 13C pyruvate magnetic resonance imaging (MRI) scan works in predicting tumor aggressiveness in patients with localized renal tumor. 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 patients with renal tumors in the future to make better treatment decisions.

Detailed Description

PRIMARY OBJECTIVES:

1. To investigate the correlation between hyperpolarized (HP) 13C pyruvate-to-lactate conversion, as measured by lactate/pyruvate ratio, and renal tumor histology (benign renal tumors versus renal cell carcinomas (RCCs)) and grade (low versus high grade in cases of RCCs).
2. To investigate the correlation between HP 13C pyruvate-to-lactate conversion, as measured by the apparent rate constant kPL, and renal tumor histology (benign renal tumors versus renal cell carcinomas (RCCs)) and grade (low versus high grade in cases of RCCs).

SECONDARY OBJECTIVES:

1. To determine the reproducibility of HP 13C pyruvate MRI in patients who undergo an optional second HP 13C pyruvate MRI.
2. To investigate the association between HP markers (peak lactate/pyruvate, lactate /pyruvate AUC, kPL, ADClac) and tissue-based markers including LDHA expression and LDH activity, and Monocarboxylate transporter 4 (MCT4) expression on tumor tissues from surgical specimen or from biopsy.
3. To determine the safety of HP 13C pyruvate in renal tumor patients

OUTLINE:

Patients receive HP 13C pyruvate intravenously (IV) and then undergo 13C MRI scan 1-2 minutes post HP 13C pyruvate injection. Patients may receive an optional second HP 13C pyruvate injection and undergo 13C pyruvate MRI scan 15 to 60 minutes following completion of the first scan.

After completion of study treatment, patients are followed up 30 minutes.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Benign Kidney Neoplasm
• Kidney Neoplasm
• Renal Cell Cancer

Intervention

• Drug: Hyperpolarized Carbon C 13 Pyruvate
  Given IV
  Other Names:

  • Hyperpolarized 13C-Pyruvate
  • Hyperpolarized Pyruvate (13C)
• Procedure: Magnetic Resonance Imaging
  Undergo MRI
  Other Names:

  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • Nuclear Magnetic Resonance Imaging

Study Arms

Experimental: Diagnostic (HP 13C pyruvate MRI)

Patients receive HP 13C pyruvate IV and then undergo 13C MRI scan 1-2 minutes post HP 13C pyruvate injection. Patients may receive an optional second HP 13C pyruvate injection and undergo 13C pyruvate MRI scan 15 to 60 minutes following completion of the first scan.

Interventions:

• Drug: Hyperpolarized Carbon C 13 Pyruvate
• Procedure: Magnetic Resonance Imaging

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2020): 100
• Original Estimated Enrollment (submitted: February 4, 2020): 40
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Localized renal tumor measuring 2 centimeters (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 2cm. We will include all localized renal tumor measuring 2 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 has a diagnostic renal tumor biopsy indicating benign histology. An increasing number of patients with small renal tumors at UCSF are referred for renal tumor biopsy and then active surveillance especially if biopsy indicates high likelihood of benign histology. We will recruit these patients into our study to ensure adequate number of benign renal tumors for this initial pilot study.
3. The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
4. The subject is willing to undergo standard of care abdominal MRI in connection with the study exam.
5. 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.
7. A history of clinically significant electrocardiogram (EKG) abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry. Patients with rate-controlled atrial fibrillation/flutter will be allowed on study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Zhen Jane Wang, MD; 415-476-3767; Zhen.Wang@ucsf.edu

Contact: Namasvi Jariwala; 415-514-6759; namasvi.jariwala@ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04258462
• Other Study ID Numbers: 18525; NCI-2018-03692 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Zhen Wang, MD, University of California, San Francisco
• Study Sponsor: Zhen Wang, MD
• Collaborators: American Cancer Society, Inc.

Investigators

• Principal Investigator: Zhen Jane Wang, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: November 2020