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

Primary Purpose

Prostate Cancer, Localized Prostate Carcinoma

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized Bicarbonate (13C)
Magnetic Resonance imaging
Sponsored by
Robert Flavell, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Prostate Cancer focused on measuring Tissue pH, Magnetic Resonance (MR) Imaging

Eligibility Criteria

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

Inclusion Criteria: Patients age >=18 years. 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. 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. Patients must have planned radical prostatectomy at UCSF within 12 weeks following protocol MRI/ magnetic resonance spectroscopy imaging) (MRSI). Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Demonstrates adequate organ function as defined below: Adequate bone marrow function: Absolute neutrophil count >=1,500 cells/µL. Platelets >=75,000 cells/µL. Hemoglobin >=9.0 gm/dL. 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. 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. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who because of general medical or psychiatric condition, or physiologic status, cannot give valid informed consent. Patients unwilling or unable to undergo MR imaging, including patients with contraindications to Magnetic resonance imaging (MRI) as per UCSF radiology departmental guidelines. 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. Patients with contra-indications to injection of gadolinium contrast as per UCSF radiology departmental guidelines. Patients who take carbonic anhydrase inhibitors (e.g. acetazolamide, dichlorphenamide, methazolamide). Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging. 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. 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. 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.

Sites / Locations

  • University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pre-surgical participants with prostate cancer

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
May 1, 2023
Last Updated
July 31, 2023
Sponsor
Robert Flavell, MD, PhD
Collaborators
U.S. Army Medical Research Acquisition Activity
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1. Study Identification

Unique Protocol Identification Number
NCT05851365
Brief Title
Magnetic Resonance (MR) Imaging With Hyperpolarized Bicarbonate (13C) to Measure Tissue pH in Prostate Cancer
Official Title
A Pilot Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Bicarbonate (13C) to Measure Tissue pH in Localized Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Flavell, MD, PhD
Collaborators
U.S. Army Medical Research Acquisition Activity

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Localized Prostate Carcinoma
Keywords
Tissue pH, Magnetic Resonance (MR) Imaging

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pre-surgical participants with prostate cancer
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized Bicarbonate (13C)
Other Intervention Name(s)
Hyperpolarized (HP) bicarbonate 13 (13C), HP C13
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance imaging
Other Intervention Name(s)
Magnetic Resonance scan, MR scan
Intervention Description
Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body
Primary Outcome Measure Information:
Title
Proportion of participants with a signal to noise ratio > 2
Description
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.
Time Frame
Day of MR imaging (1 day)
Secondary Outcome Measure Information:
Title
Percentage of participants with reported treatment-emergent adverse events
Description
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.
Time Frame
Up to 9 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients age >=18 years. 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. 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. Patients must have planned radical prostatectomy at UCSF within 12 weeks following protocol MRI/ magnetic resonance spectroscopy imaging) (MRSI). Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Demonstrates adequate organ function as defined below: Adequate bone marrow function: Absolute neutrophil count >=1,500 cells/µL. Platelets >=75,000 cells/µL. Hemoglobin >=9.0 gm/dL. 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. 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. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who because of general medical or psychiatric condition, or physiologic status, cannot give valid informed consent. Patients unwilling or unable to undergo MR imaging, including patients with contraindications to Magnetic resonance imaging (MRI) as per UCSF radiology departmental guidelines. 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. Patients with contra-indications to injection of gadolinium contrast as per UCSF radiology departmental guidelines. Patients who take carbonic anhydrase inhibitors (e.g. acetazolamide, dichlorphenamide, methazolamide). Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging. 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. 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maya Aslam
Phone
(415) 514-8987
Email
Maya.Aslam@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Flavell, MD, PhD
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
Maya Aslam
Phone
415-514-8987
Email
Maya.Aslam@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Robert Flavell, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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