Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Hyperpolarized 13C Pyruvate, Pancreatic Cancer
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
Interventions
Given IV prior to imaging
PROCEDUREMagnetic Resonance Imaging (MRI)
Undergo MRI
Sponsors
Zhen Wang, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort B: Target Tumor Metabolism | Up to 4 weeks | 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. |
| Cohort A: Signal-to-noise Ratio of the Target Lesion 13C Pyruvate Metabolism Measures Will be Determined for Each Patient | Baseline | Descriptive statistics will be used to summarize the mean, standard deviation, and 95% confidence interval of the measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Intraclass Correlation Coefficient (ICC) | Up to 6 months | 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 |
| Cohort B: Best Objective Response | Up to 4 weeks after treatment initiation | 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. |
Countries
United States
Participant flow
Pre-assignment details
No participants were assigned to Cohort A based on diagnosis
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Single Dose/Image Participants receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute then undergo MRI over 5 minutes at baseline | 0 |
| Cohort B: Multiple Dose/Images Participants 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 | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Cohort A: Single Dose/Image | Cohort B: Multiple Dose/Images | Total |
|---|---|---|---|
| Age, Customized 50-59 years old | 0 Participants | 2 Participants | 2 Participants |
| Age, Customized 60-69 years old | 0 Participants | 4 Participants | 4 Participants |
| Age, Customized 70-79 years old | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | — | 7 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 7 |
| other Total, other adverse events | 0 / 0 | 0 / 7 |
| serious Total, serious adverse events | 0 / 0 | 0 / 7 |
Outcome results
Primary
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.
Time frame: Baseline
Population: No participants were enrolled to Cohort A
Primary
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.
Time frame: Up to 4 weeks
Population: Data was not collected for this endpoint
Secondary
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
Time frame: Up to 6 months
Population: No participants were enrolled to Cohort A
Secondary
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.
Time frame: Up to 4 weeks after treatment initiation
Population: Data was not collected for this endpoint