This will be a single-arm, multi-center, open-label phase 1 study. The standard 3+3 design will be used to determine the maximum tolerated dose (MTD) from 4 possible dose levels of Eryaspase in combination with mFOLFIRINOX. We hypothesize that the addition of Eryaspase to FOLFIRINOX (5-fluorouracil \[5-FU\], leucovorin, irinotecan, and oxaliplatin) will be safe and demonstrate preliminary signs of efficacy in patients with advanced pancreatic cancer. Safety assessments include adverse events, physical examination abnormalities, vital signs, and clinical laboratory tests (including blood chemistry, hematology, and coagulation panel).
This is an open-label, multicenter, Phase 1 study of Eryaspase combination with FOLFIRINOX in patients with locally advanced or metastatic pancreatic adenocarcinoma. Subjects will undergo screening in order to determine eligibility. The study will use a standard 3+3 method of dose escalation. Patients will be enrolled in cohorts of 3. Four dose levels are planned and include 25, 50, 75, and 100 mg of Eryaspase with reduced dose irinotecan. Subjects will be assigned to a dose level in the order of study entry with at least a 3-day stagger in enrollment between individual subjects. With the 3+3 design to be employed, doses are not escalated unless all patients receiving the current dose have been observed for at least 6 weeks and dose-limiting toxicities (DLTs) have been reported. The MTD is defined as the highest dose level where at most 1 of 6 patients experience a dose limiting toxicity (DLT). Three patients will be treated at dose level 0. If 0/3 experience a DLT, 3 new patients will be enrolled at the next higher dose level. If 1/3 experience a DLT, 3 additional patients will be enrolled at the same dose level. If 1/6 patients experience a DLT at any dose level except the highest dose level, 3 new patients will be enrolled at the next higher dose level; if 1/6 patients at the highest dose level experience a DLT, it will be deemed the MTD and the trial will stop. As soon as 2 patients experience a DLT at a given dose level, that dose will be concluded to be above the MTD, dose escalation will cease and 3 new patients will be enrolled at the next lower dose level. If 6 patients were previously treated at that lower dose, the study will halt and that lower dose will be declared the MTD. A subject who withdraws from the escalation phase of the study for reasons other than a DLT will be replaced. FOLFIRINOX treatment will be given on Day 1 and 15 of the 4 weeks cycle and continued until unacceptable toxicity or disease progression, for a maximum of 12 cycles. Subjects will receive a single intravenous administration of Eryaspase on Day 1 and 15 of 4-weeks cycle. The study visits are day 1, 8, 15, 22, during cycle 1 and day 1 and 15 during subsequent cycles with a 4-week follow-up period after the end of treatment. Subjects who show at least stable disease based on RECIST 1.1 at the end of the 12-week period (Day 85) are eligible for the continuation of FOLFIRINOX plus eryaspase treatment until disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
intravenous administration of Eryaspase, starting dose 75 units/kg, dose escalation to 100 units/kg, dose reduction 50 units/kg and 25 units/kg
intravenous administration of FOLFIRINOX
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, United States
Incidence of Grade 3 or 4 Adverse Events
The number (percentage) of all subjects who experience Grad 3 or 4 treatment emergent adverse events (AEs), serious adverse events (SAEs), or abnormal laboratory results according to NCI CTCAE Version 5.0, that occur after Cycle 1, Day 1 will be reported until end of treatment visit.
Time frame: 1 year
Objective Response Rate by RECIST 1.1
Number of participants with a complete or partial response from treatment as assessed by CT scan per RECIST 1.1 criteria.
Time frame: 2 years
Progression-free Survival (PFS)
Time in months from start of treatment to disease progression, death, or completion of study which ever occurred first.
Time frame: 3 years
Overall Survival (OS)
The length of time from treatment initiation until death from any cause or off study date, whichever occurs first.
Time frame: 3 years
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