The purpose of this research is to observe the effects of using a new combination of drugs to inhibit tumor growth.
The patients will undergo testing, exams, and procedures per the Protocol. On study, patients will be randomized into one of the two arms. In Arm A (up to 15 patients) will be treated with modified FOLFIRINOX every two weeks, delivered as follows: * Oxaliplatin 85mg/m2 IV over 2 hours on Day 1, followed by, * Irinotecan 150mg/m2 IV over 90 minutes on Day 1, followed by * Leucovorin 400mg/m2 IV over 2 hours on Day 1, followed by * 5FU 2400mg/m2 IV over 46-48 hours on Days 1-3 In arm B patients (up to 15), the same modified FOLFIRINOX regimen will be used, as above, plus 300 mg pentamidine will be administered IV over a one-hour infusion on Day 1 of each cycle. In both arms, patients will be treated over eight two-week cycles, and the entire treatment is expected to last approximately 4 months. After eight cycles, patients will undergo another EUS core biopsy. At the same time as the biopsy, an additional blood draw (for translational endpoints) will be done. After the biopsy, patients will continue treatment per physician's discretion for an additional 2 months (or 4 cycles) for a total of 12 cycles (or 6 months of treatment) until disease progression or appearance of unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
In Arm A (up to 15 patients) will be treated with modified FOLFIRINOX every two weeks, delivered as follows: * Oxaliplatin 85mg/m2 IV over 2 hours on Day 1, followed by, * Irinotecan 150mg/m2 IV over 90 minutes on Day 1, followed by * Leucovorin 400mg/m2 IV over 2 hours on Day 1, followed by * 5FU 2400mg/m2 IV over 46-48 hours on Days 1-3
In arm B patients (up to 15), the same modified FOLFIRINOX regimen will be used, as above, plus 300 mg pentamidine will be administered IV over a one-hour infusion on Day 1 of each cycle.
University of Oklahoma Health Campus
Oklahoma City, Oklahoma, United States
Number and proportion of patients with Grade 3 and higher adverse events deemed related to pentamidine during trial treatment, using CTCAE v.6.0.
To evaluate the safety in patients with metastatic or nonresectable locally advanced pancreatic cancer treated with modified FOLFIRINOX (arm A) versus modified FOLFIRINOX plus Pentamidine (arm B)
Time frame: 3 years
Evaluation of the objective response rate in modified FOLFIRINOX (arm A) versus modified FOLFIRINOX plus Pentamidine (arm B)
Proportion of patients with Objective response rate and partial response as measured by RECIST version 1.1 to be evaluated by imaging study and radiology review.
Time frame: 3 years
Evaluation of the rate of progression-free survival in both arms
Proportion of patients with a response rate measurement of Progression-free survival determined by the number of days from the start of study treatment to date of imaging-confirmed tumor progression, death or last time of follow up
Time frame: 3 years
Evaluation of the duration of response in both arms
Proportion of patients with Duration of response determined as the number of days from the onset of the first response to disease progression or death
Time frame: 3 years
Evaluation of genetic mutations that predict patient response to modified FOLFIRINOX plus Pentamidine
Proportion of patients with expression levels of MUC1, SAT1, and other metabolic genes by performing transcriptomic analysis of biopsies.
Time frame: 3 years
Evaluation of potential utility of N1-acetylspermidine and nucleotide pools as a biomarker of efficacy of the combination therapy.
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Proportion of patients with circulating N'acetylspermidine1levels, other circulating polyamines levels, tumor tissue uptake of pentamidine by quantitating N1-acetylspermidine levels by liquid chromatography-coupled tandem mass spectrometry, and quantitate nucleotide pools in biopsy tissues by liquid chromatography-coupled tandem mass spectrometry
Time frame: 3 years