This study will enroll a total of 16 patients with advanced pancreatic cancer at Cedars-Sinai Medical Center. All subjects will receive combination therapy of gemcitabine, nab-paclitaxel, and L-glutamine. The study investigates what the appropriate dosage of L-glutamine is so that there is the lowest risk of side effects, and whether the supplement will make standard chemotherapy of gemcitabine and nab-paclitaxel more effective in treating advanced pancreatic cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Gemcitabine will be administered at 600, 800, or 1000 mg/m2 intravenous (IV) infusion over 30 minutes on days 1, 8, and 15 (every 28-day cycles) during the treatment period. Gemcitabine will be administered immediately after the infusion of nab-paclitaxel. Pre-medication with may be administered per institutional standard practice at the investigator's discretion with gemcitabine.
Nab-paclitaxel will be administered at 75, 100, or 125 mg/m2 intravenous (IV) infusion over 30 minutes on days 1, 8, and 15 (every 28-day cycles) during the treatment period. Nab-paclitaxel will be given first, before infusion of gemcitabine. Pre-medication for nab-paclitaxel may be administered per institutional standard practice at investigator's discretion.
The dose levels of L-glutamine in this study will be 0.1, 0.2, and 0.3 g/kg oral twice daily (rounded to nearest 5 g with an upper limit of 15 g twice daily (30 g/day) for any dose level) taken at the same time each day during the treatment period. L-glutamine will be administered for 1 week (+/-1 day) prior to addition of gemcitabine/nab-paclitaxel. Each dose of L-glutamine should be mixed immediately before ingestion with 8 oz. (240 mL) of a cold or room temperature beverage, such as water, milk or apple juice, or 4 oz. (120 mL) to 6 oz. (177 mL) of food such as applesauce or yogurt. L-glutamine is formulated in 5 gram packets as a white crystalline powder in paper-foil-plastic laminate. Complete dissolution is not required prior to administration.
Tower Hematology Oncology Medical Group (THO)
Beverly Hills, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
Recommended phase II dose (RP2D) of combination gemcitabine, nab-paclitaxel, and L-glutamine in treatment-naive metastatic pancreatic cancer.
The number of dose-limiting toxicities (DLTs), defined as the rate of drug-related grade ≥3 adverse events (AEs) experienced within the first 4 weeks (1 cycle) of study treatment. The RP2D is defined as the dose level closest to the median of the posterior distribution of the maximum tolerated dose (MTD). The MTD is defined as the dose level such that the probability of DLT at the MTD is θ=0.33.
Time frame: 4 weeks
Describe the safety of gemcitabine, nab-paclitaxel and L-glutamine across all investigated dose levels in subjects with untreated advanced pancreatic cancer
Number of adverse events as assessed by NCI CTCAE version 5.0
Time frame: From first dose of study treatment until 30 days after the last dose of study treatment (up to approximately 12 months)..
Describe any preliminary evidence of antitumor activity of the combination by assessment of objective response rate as determined by RECIST 1.1 criteria in patients with measurable disease.
Clinical activity of the combination including objective response rate (ORR), defined as proportion of patients with confirmed PR or CR, evaluated every 8 weeks (every 2 cycles ±1 week) according to the revised RECIST guidelines (version 1.1)
Time frame: From screening/baseline until the last dose of study treatment (up to approximately 12 months).
Describe any preliminary evidence of antitumor activity of the combination by assessment of progression-free survival as determined by RECIST 1.1 criteria in patients with measurable disease.
Clinical activity of the combination including progression-free survival (PFS), defined as from baseline until date of progression or death due to any cause, evaluated every 8 weeks (every 2 cycles ±1 week) according to the revised RECIST guidelines (version 1.1).
Time frame: From screening/baseline until the last dose of study treatment (up to approximately 12 months).
Describe any preliminary evidence of antitumor activity of the combination by assessment of overall survival as determined by RECIST 1.1 criteria in patients with measurable disease.
Clinical activity of the combination including overall survival (OS), defined as from baseline until date of death due to any cause, evaluated every 8 weeks (every 2 cycles ±1 week) according to the revised RECIST guidelines (version 1.1).
Time frame: From screening/baseline until the last dose of study treatment (up to approximately 12 months).
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