Magnetic Resonance (MR) Imaging With Hyperpolarized Bicarbonate (13C) to Measure Tissue pH in Prostate Cancer

A Pilot Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Bicarbonate (13C) to Measure Tissue pH in Localized Prostate Cancer

This is a single site, prospective pilot study to determine the feasibility and safety of the administration of HP 13C bicarbonate in 10 patients with prostate cancer to determine potential hydrogen (pH) values in surrounding tissue. The proposed study will evaluate pre-surgical participants with histologically confirmed localized prostate cancer who receive infusion of hyperpolarized 13C injection prior to MR imaging with endorectal coil.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Localized Prostate Carcinoma
• Intervention / Treatment: Drug: Hyperpolarized Bicarbonate (13C); Procedure: Magnetic Resonance imaging

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the feasibility of tumor pH measurement in men with prostate cancer using hyperpolarized 13C bicarbonate imaging.

SECONDARY OBJECTIVE:

I. To determine the safety of administration of hyperpolarized 13C-bicarbonate.

OUTLINE:

Men with biopsy-proven adenocarcinoma of the prostate scheduled to undergo radical prostatectomy at University of California, San Francisco (UCSF) within 12 weeks of enrollment will receive infusion with hyperpolarized 13C bicarbonate and undergo metabolic MR imaging with endorectal coil. Participants will be followed for 5-9 days after the hyperpolarized 13C-bicarbonate injection, or removal from study, or until death, whichever occurs first. Participants removed from study for unacceptable study related adverse event(s) will be followed until resolution or stabilization (as determined by the investigator) or until initiation of new anti-cancer therapy, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Maya Aslam; Phone Number: (415) 514-8987; Email: Maya.Aslam@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Robert Flavell, MD, PhD
      • Contact: Maya Aslam; Phone Number: 415-514-8987; Email: Maya.Aslam@ucsf.edu
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients age >=18 years.
2. Patients must have biopsy-proven adenocarcinoma of the prostate; biopsy may be performed outside of University of California, San Francisco (UCSF) if detailed results of sextant biopsy are available.
3. Tumor size of at least 1.0 cm in long axis on Magnetic resonance imaging (MRI) or ultrasound; if no prior imaging is available, at least 3 cores positive on biopsy.
4. Patients must have planned radical prostatectomy at UCSF within 12 weeks following protocol MRI/ magnetic resonance spectroscopy imaging) (MRSI).
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

6. Demonstrates adequate organ function as defined below:

   1. Adequate bone marrow function:

      • Absolute neutrophil count >=1,500 cells/µL.
      • Platelets >=75,000 cells/µL.
      • Hemoglobin >=9.0 gm/dL.

   2. Adequate hepatic function:

      • Total bilirubin <1.5x upper limits of normal (ULN) (within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits).
      • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) <=1.5 X institutional upper limit of normal.
      • Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <=1.5 X institutional upper limit of normal.

   3. Adequate renal function:

      • Creatinine clearance >= 50 calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2.
7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who because of general medical or psychiatric condition, or physiologic status, cannot give valid informed consent.
2. Patients unwilling or unable to undergo MR imaging, including patients with contraindications to Magnetic resonance imaging (MRI) as per UCSF radiology departmental guidelines.
3. Patients who cannot tolerate or have contra-indications to endorectal coil insertion, for example, patients with a prior abdominoperineal resection of the rectum or latex allergy.
4. Patients with contra-indications to injection of gadolinium contrast as per UCSF radiology departmental guidelines.
5. Patients who take carbonic anhydrase inhibitors (e.g. acetazolamide, dichlorphenamide, methazolamide).
6. Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
7. Cryosurgery, surgery for prostate cancer, prostatic or pelvic radiotherapy prior to study enrollment. No limit on number of prior prostate biopsies. Prior Transurethral Resection of the Prostate (TURP) is not allowed.
8. 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.
9. Congestive heart failure or New York Heart Association (NYHA) status >= 2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-surgical participants with prostate cancer; The hyperpolarized 13C bicarbonate injection includes the administration of 35 mL injected intravenously (IV) at a rate of 5 mL/second followed by a 20 mL saline flush at 5 mL/second, followed by magnetic resonance (MR) imaging. The intervention will include routine and safety assessments 5 to 9 days after the injection.	Drug: Hyperpolarized Bicarbonate (13C); Given IV; Other Names: Hyperpolarized (HP) bicarbonate 13 (13C); HP C13; Procedure: Magnetic Resonance imaging; Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body; Other Names: MR scan; Magnetic Resonance scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a signal to noise ratio > 2	The feasibility of a study will be determined by the ability to generate adequate signal to noise ratio to measure acidity (pH) in tumor or adjacent healthy tissue. This study will be considered successful if the 13C bicarbonate (CO2) and 13C-CO2 resonances in tumor or normal prostate are qualitatively detectable and signal to noise ratios are greater than 2. The point estimation and 95% confidence intervals (CI) of the participants having sufficient signal to noise ratio will be obtained using the Wilson Score confidence interval method.	Day of MR imaging (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with reported treatment-emergent adverse events	To assess the safety of the administration of hyperpolarized 13C bicarbonate; adverse events will be collected and recorded by type, severity (grade) and attribution according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The percentage of participants with grade 2 and higher, treatment-emergent adverse events will be reported.	Up to 9 days

Collaborators and Investigators

• Sponsor: Robert Flavell, MD, PhD
• Collaborators: U.S. Army Medical Research Acquisition Activity
• Investigators: Principal Investigator: Robert Flavell, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Tissue pH; Magnetic Resonance (MR) Imaging
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 23922; NCI-2023-03218 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No