Clinical trial NCT04565327: Hyperpolarized 13C Pyruvate MRI for Treatment Response Assessment in Pancreatic Ductal Adenocarcinoma
Official title: Hyperpolarized 13C Pyruvate MRI for Treatment Response Assessment in Pancreatic Ductal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Keywords: Hyperpolarized 13C Pyruvate
Pancreatic Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This phase II trial investigates whether magnetic resonance imaging (MRI) using hyperpolarized carbon-13 (13C) pyruvate can be useful for evaluating early treatment response in patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) or spread to other places in the body (metastatic). Hyperpolarized 13C pyruvate is different from standard clinical MRI contrast (e.g. gadolinium) in that it provides information on how a tumor processes nutrients. MRI is used to see tumor uptake and breakdown of hyperpolarized carbon-13 pyruvate molecules, which can tell how the tumor processes nutrients. Hyperpolarized 13C pyruvate MRI may help in understanding how the tumor responds to the treatments patients may be receiving.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the signal-to-noise ratio of 13C pyruvate metabolism (peak 13C lactate/pyruvate ratio, 13C lactate/pyruvate area-under-the-curve (AUC) ratio, and apparent rate constant for pyruvate-to-lactate conversion, kPL) in the target tumor (primary tumor and/or abdominal metastases) in Cohort A.

II. To determine the percent changes in the target tumor (primary tumor and/or abdominal metastases) 13C pyruvate metabolism (peak 13C lactate/pyruvate ratio, 13C lactate/pyruvate AUC ratio, and kPL) between pre-treatment scan and scan obtained at 4-week (+/-2 weeks) following treatment initiation in Cohort B.

SECONDARY OBJECTIVES:

I. To determine the repeatability of 13C pyruvate metabolism measures in the target tumor (primary tumor and/or abdominal metastasis) in patients with same-day repeated dose in Cohort A and B.

II. To determine whether the baseline or the changes in the target tumor (primary tumor and/or abdominal metastases) 13C pyruvate metabolism at 4 weeks following treatment initiation are associated with the best objective response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria on subsequent clinical computed tomography (CT) scans in Cohort B.

EXPLORATORY OBJECTIVE:

I. To explore 13C pyruvate metabolism between the primary tumor and abdominal metastases (when present) both at baseline and following treatment in both Cohort A and B.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute then undergo MRI over 5 minutes at baseline in the absence of unacceptable toxicity.

COHORT B: Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute then undergo MRI over 5 minutes at baseline and 4 weeks after beginning treatment in the absence of unacceptable toxicity.

In both cohorts, patients may receive an optional second hyperpolarized carbon C 13 pyruvate dose and undergo MRI within 15 to 60 minutes following the completion of the first scan.

After completion of study treatment, patients are followed up every 2-3 months

Eligibility criteria: Inclusion Criteria:

* Locally advanced or metastatic pancreatic ductal adenocarcinoma, with at least one target lesion in the abdomen measuring \>= 1 cm
* The subject 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

Exclusion Criteria:

* Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent
* Patients unwilling or unable to undergo magnetic resonance (MR) imaging, including patients with contraindications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips
* Poorly controlled hypertension, defined as either systolic \> 170 or diastolic \> 110. The addition of anti-hypertensives to control blood pressure is allowed for eligibility determination
* Congestive heart failure \>= class III
* Myocardial infarction within the past year
* History of QT prolongation on electrocardiogram (EKG), defined as pretreatment QTs \> 440 msec in males or \> 460 msec in females
* Pregnant and lactating females

Primary outcomes:
measure: Cohort A: Signal-to-noise Ratio of the Target Lesion 13C Pyruvate Metabolism Measures Will be Determined for Each Patient
timeFrame: Baseline
measure: Cohort B: Target Tumor Metabolism
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Cohort A: Intraclass Correlation Coefficient (ICC)
timeFrame: Up to 6 months
measure: Cohort B: Best Objective Response
timeFrame: Up to 4 weeks after treatment initiation
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Zhen Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: