search
Back to results

Hyperpolarized 13C Pyruvate as a Biomarker in Advanced Solid Tumors

Primary Purpose

Advanced Solid Tumor

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hyperpolarized 13C-Pyruvate
Magnetic Resonance Imaging (MRI)
Sponsored by
Robert Bok, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Biomarker

Eligibility Criteria

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

Inclusion Criteria: Presence of at least one target pelvic, abdominal, thoracic, neck or extremity lesion detected by standard staging scans that, in the judgment of study investigator, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging: a. Target lesion must measure at least 1.0 cm in long axis diameter on Computerized tomography (CT) or magnetic resonance imaging (MRI). The participant is able and willing to comply with study procedures and provide signed and dated informed consent. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Adequate renal function defined as creatinine < 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >50 mL/min (by the Cockcroft Gault equation). Participants age 18 and older. Part B only: Planned treatment for disease with either standard of care regimen or an investigational agent. Exclusion Criteria: Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent. Patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips. Patients with a metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging. Patients with poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160mm Hg or diastolic blood pressure greater than 100mm Hg. Note: The addition of anti-hypertensives to control blood pressure is allowed. Patients with congestive heart failure or New York Heart Association (NYHA) status >= 2. Patients who are pregnant or lactating. A history of clinically significant EKG abnormalities or myocardial infarction (MI) within 6 months of study entry. Note: Patients with rate-controlled atrial fibrillation/flutter will be allowed on study. Any condition that, in the opinion of the Principal Investigator,

Sites / Locations

  • University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A / Phase 1: Feasibility Run-In

Part B/ Phase II: Biomarker Cohort

Arm Description

Participants will undergo MR imaging at a single time point. Imaging will take one day. and no follow up is planned.

Participants will undergo paired hyperpolarized pyruvate/metabolic MR imaging at baseline and again after approximately 21 days of the participants SOC or investigational therapy outside of this protocol.

Outcomes

Primary Outcome Measures

Signal-to-noise ratio (Part A)
Signal-to-noise ratios is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue. For the analysis and interpretation of the HP 13C-pyruvate MR imaging data, DICOM software package (SIVIC) will be used to align, display and quantitatively interrogate serial multi-parametric imaging data.
Mean percent change from baseline in intratumoral HP pyruvate/lactate ratio
Intra-tumoral region of interest (ROI) will be used to quantify peak HP lactate/pyruvate ratio values in the selected volumes of interest. Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio for the study cohort, along with a 95% confidence interval

Secondary Outcome Measures

Number of participants reporting adverse events (Part A)
Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Number of participants reporting adverse events (Part B)
Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B)
Lactate/pyruvate ratio: hyperpolarized Lactate signal divided by the hyperpolarized pyruvate signal within the tumor region, for each injection/scan on the same day.
Objective response rate (ORR) (Part B)
ORR is defined as the proportion of treated patients who experience an objective response (confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Clinical benefit rate (CBR) (Part B)
CBR is defined as the proportion of treated patients who experience clinical benefit (confirmed complete response (CR); confirmed partial response (PR); or stable disease (SD) for > 24 weeks per RECIST 1.1 criteria).
Radiographic progression-free survival (rPFS) (Part B)
rPFS is defined as the amount of time that elapses between initiation of standard of care treatment and the day of first documented radiographic disease progression per RECIST v.1.1 or death from any cause.
Lactate/pyruvate ratio (Part B)
Intra-patient reproducibility of HP lac/pyr ratio and kPL for patients who undergo repeated dose imaging studies will be descriptively reported using summary statistics (mean difference, standard deviation, range).

Full Information

First Posted
October 25, 2022
Last Updated
December 16, 2022
Sponsor
Robert Bok, MD, PhD
Collaborators
National Institute for Biomedical Imaging and Bioengineering (NIBIB), National Cancer Institute (NCI), Sigma-Aldrich
search

1. Study Identification

Unique Protocol Identification Number
NCT05599048
Brief Title
Hyperpolarized 13C Pyruvate as a Biomarker in Advanced Solid Tumors
Official Title
A Phase I/II Study of Hyperpolarized 13C Pyruvate as a Biomarker of Aggressiveness & Response to Therapy in Patients With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2022 (Actual)
Primary Completion Date
January 31, 2026 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Bok, MD, PhD
Collaborators
National Institute for Biomedical Imaging and Bioengineering (NIBIB), National Cancer Institute (NCI), Sigma-Aldrich

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 center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate/metabolic MR imaging. The current protocol will serve as a companion imaging biomarker study paired with standard of care (SOC) therapeutics, as well as investigational therapies that participants may be scheduled to receive outside of this protocol.
Detailed Description
PRIMARY OBJECTIVES: Phase I/Part A 1. To optimize the signal-to-noise ratio in detecting intra-tumoral hyperpolarized 13C pyruvate/lactate signal using metabolic MR imaging in participants with advanced solid tumors. Phase II/Part B 1. To determine the mean percent change from baseline in peak intra-tumoral hyperpolarized lactate-to-pyruvate ratio and pyruvate-to-lactate kinetic constant (kPL) after initiation of SOC treatment. SECONDARY OBJECTIVES: Phase I/Part A To further characterize the safety profile of hyperpolarized 13C-pyruvate. To determine the reproducibility of intra-tumoral HP lac/pyr ratio with same-day repeated dose studies. Phase II/Part B To study the association between clinical outcomes and the percent change from baseline in peak intra-tumoral hyperpolarized lactate-to-pyruvate ratio and kPL after initiation of SOC treatment. To further characterize the safety profile of hyperpolarized 13C pyruvate. To determine the reproducibility of intra-tumoral HP lac/pyr ratio with same-day repeated dose studies. OUTLINE: Participants will be enrolled in Part A which is the feasibility, run-in study which includes the iterative adjustment of coil design to optimize imaging parameters within the target tumor lesion(s). If the data from Part A supports further investigation, additional participants will be enrolled in Part B which is a biomarker cohort which includes participants who are planning on being treated with either standard-of-care (SOC) or investigational therapies and will be followed until discontinuation of the treatment regimen outside of this protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor
Keywords
Biomarker

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A / Phase 1: Feasibility Run-In
Arm Type
Experimental
Arm Description
Participants will undergo MR imaging at a single time point. Imaging will take one day. and no follow up is planned.
Arm Title
Part B/ Phase II: Biomarker Cohort
Arm Type
Experimental
Arm Description
Participants will undergo paired hyperpolarized pyruvate/metabolic MR imaging at baseline and again after approximately 21 days of the participants SOC or investigational therapy outside of this protocol.
Intervention Type
Drug
Intervention Name(s)
Hyperpolarized 13C-Pyruvate
Other Intervention Name(s)
Hyperpolarized (HP) carbon^13 (13C)-pyruvate, HP-13C
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging (MRI)
Other Intervention Name(s)
MRI
Intervention Description
Imaging procedure
Primary Outcome Measure Information:
Title
Signal-to-noise ratio (Part A)
Description
Signal-to-noise ratios is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue. For the analysis and interpretation of the HP 13C-pyruvate MR imaging data, DICOM software package (SIVIC) will be used to align, display and quantitatively interrogate serial multi-parametric imaging data.
Time Frame
Day of imaging (1 day)
Title
Mean percent change from baseline in intratumoral HP pyruvate/lactate ratio
Description
Intra-tumoral region of interest (ROI) will be used to quantify peak HP lactate/pyruvate ratio values in the selected volumes of interest. Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio for the study cohort, along with a 95% confidence interval
Time Frame
Up to 21 days
Secondary Outcome Measure Information:
Title
Number of participants reporting adverse events (Part A)
Description
Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame
Day of imaging (1 day)
Title
Number of participants reporting adverse events (Part B)
Description
Safety analyses will be performed for all patients having received a dose of HP 13C pyruvate. Adverse events will be classified and graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame
Up to 6 months
Title
Median percent change from baseline in peak intratumoral hyperpolarized lactate-to-pyruvate ratio (Part B)
Description
Lactate/pyruvate ratio: hyperpolarized Lactate signal divided by the hyperpolarized pyruvate signal within the tumor region, for each injection/scan on the same day.
Time Frame
Up to 6 months
Title
Objective response rate (ORR) (Part B)
Description
ORR is defined as the proportion of treated patients who experience an objective response (confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
Up to 6 months
Title
Clinical benefit rate (CBR) (Part B)
Description
CBR is defined as the proportion of treated patients who experience clinical benefit (confirmed complete response (CR); confirmed partial response (PR); or stable disease (SD) for > 24 weeks per RECIST 1.1 criteria).
Time Frame
Up to 6 months
Title
Radiographic progression-free survival (rPFS) (Part B)
Description
rPFS is defined as the amount of time that elapses between initiation of standard of care treatment and the day of first documented radiographic disease progression per RECIST v.1.1 or death from any cause.
Time Frame
Up to 6 months
Title
Lactate/pyruvate ratio (Part B)
Description
Intra-patient reproducibility of HP lac/pyr ratio and kPL for patients who undergo repeated dose imaging studies will be descriptively reported using summary statistics (mean difference, standard deviation, range).
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Presence of at least one target pelvic, abdominal, thoracic, neck or extremity lesion detected by standard staging scans that, in the judgment of study investigator, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging: a. Target lesion must measure at least 1.0 cm in long axis diameter on Computerized tomography (CT) or magnetic resonance imaging (MRI). The participant is able and willing to comply with study procedures and provide signed and dated informed consent. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Adequate renal function defined as creatinine < 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >50 mL/min (by the Cockcroft Gault equation). Participants age 18 and older. Part B only: Planned treatment for disease with either standard of care regimen or an investigational agent. Exclusion Criteria: Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent. Patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips. Patients with a metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging. Patients with poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160mm Hg or diastolic blood pressure greater than 100mm Hg. Note: The addition of anti-hypertensives to control blood pressure is allowed. Patients with congestive heart failure or New York Heart Association (NYHA) status >= 2. Patients who are pregnant or lactating. A history of clinically significant EKG abnormalities or myocardial infarction (MI) within 6 months of study entry. Note: Patients with rate-controlled atrial fibrillation/flutter will be allowed on study. Any condition that, in the opinion of the Principal Investigator,
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Louise Magat
Phone
(415) 502-1822
Email
Louise.Magat@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Bok, 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
Louise Magat
Phone
415-502-1822
Email
Louise.Magat@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Robert Bok, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Hyperpolarized 13C Pyruvate as a Biomarker in Advanced Solid Tumors

We'll reach out to this number within 24 hrs