Hyperpolarized 13C Pyruvate MRI for Treatment Response Assessment in Pancreatic Ductal Adenocarcinoma

Study Overview
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Brief Summary
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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
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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

Official Title
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Hyperpolarized 13C Pyruvate MRI for Treatment Response Assessment in Pancreatic Ductal Adenocarcinoma

Conditions
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Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: Hyperpolarized Carbon C 13 Pyruvate
* Procedure: Magnetic Resonance Imaging (MRI)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Single Dose/Image<br>Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute then undergo MRI over 5 minutes at baseline | Drug: Hyperpolarized Carbon C 13 Pyruvate<br>* Given IV prior to imaging<br>* Other names: Hyperpolarized 13C Pyruvate;Procedure: Magnetic Resonance Imaging (MRI)<br>* Undergo MRI<br>* Other names: MR Imaging;|
| Experimental: Cohort B: Multiple Dose/Images<br>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 | Drug: Hyperpolarized Carbon C 13 Pyruvate<br>* Given IV prior to imaging<br>* Other names: Hyperpolarized 13C Pyruvate;Procedure: Magnetic Resonance Imaging (MRI)<br>* Undergo MRI<br>* Other names: MR Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Signal-to-noise Ratio of the Target Lesion 13C Pyruvate Metabolism Measures Will be Determined for Each Patient | Descriptive statistics will be used to summarize the mean, standard deviation, and 95% confidence interval of the measurements. | Baseline | 
| Cohort B: Target Tumor Metabolism | Paired t-test or Wilcoxon signed rank test will be used to compare the target tumor Hyperpolarized (HP) 13C pyruvate metabolism pre- and 4-week (+/- 2 weeks) post treatment initiation. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Intraclass Correlation Coefficient (ICC) | ICC will be used to estimate the intra-subject agreement to assess repeatability of tumor HP 13C pyruvate metabolism in patients with same-day repeated dose. ICC will also be used to estimate agreement obtained from a one-way analysis of variance model based on 2 measurements per subject. The result will be presented with a 95% confidence interval | Up to 6 months | 
| Cohort B: Best Objective Response | Objective response for patients in Cohort B will be defined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on subsequent clinical CT scans. For the purpose of response assessment in this pilot study, we will group patients either as having disease control when the best response is complete response (CR), partial response (PR), or stable disease (SD) on subsequent clinical CT scans, or having disease progression when the best response is progressive disease (PD) on subsequent CT scans. Comparisons the baseline or changes in the target tumor 13C pyruvate metabolism at 4 weeks (+/-2 weeks) after treatment initiation between the disease control group and disease progression group (as defined by RECIST on subsequent clinical CT scans) will be made using the Mann-Whitney tests. | Up to 4 weeks after treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperpolarized 13C Pyruvate, Pancreatic Cancer