Description:
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).
Title
- Brief Title: Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma
- Official Title: A Phase I Dose Escalation Study of Eryaspase in Combination With Modified FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Ductal Adenocarcinoma
Clinical Trial IDs
- ORG STUDY ID:
STUDY00002008
- NCT ID:
NCT04292743
Conditions
- Locally Advanced Pancreatic Ductal Adenocarcinoma
- Metastatic Pancreatic Ductal Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
Eryaspase | | Eryaspase plus FOLFIRINOX |
FOLFIRINOX | 5-fluorouracil, oxaliplatin, Irinotecan, leucovorin | Eryaspase plus FOLFIRINOX |
Purpose
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).
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Eryaspase plus FOLFIRINOX | Experimental | Eryaspase will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion) in dose escalating/reduction depending on the cohort the patient is assigned to
mFOLFIRINOX dosing will include 5-fluorouracil 2400 mg/m² over 46 hours, oxaliplatin 85 mg/m², Irinotecan 150 mg/m² (intravenous infusion) on Day 1 and 15 of the 4 weeks cycle for a maximum of 12 cycles. | |
Eligibility Criteria
Inclusion Criteria:
- Patient must be able to understand and willing to sign an IRB approved written
informed consent document.
- Patient must have histologically or cytologically confirmed pancreatic adenocarcinoma,
which is locally advanced, unresectable, or metastatic.
- Patient must have received no previous surgery, chemotherapy, radiotherapy or
investigational therapy for the treatment of locally advanced or metastatic disease.
- If a patient has had adjuvant/neoadjuvant therapy for localized disease, tumor
recurrence or disease progression must have occurred no sooner than 6 months after
completing the last dose of the aforementioned therapies.
- Patient must have radiographically measurable disease according to RECIST 1.1
- Patient must be > 18 years of age.
- Patient must have a life expectancy of >= 3 months.
- Patient must have an ECOG performance status ≤ 1.
- Patient must have normal bone marrow and organ function as defined below:
- Absolute neutrophil count >=1,500/mcl
- Platelets >=100,000/mcl
- Hemoglobin >=9.0 g/dL
- Serum Albumin >=3.0 g/dL
- Creatinine should be below the upper limit of normal OR Creatinine clearance
(eGFR) >=60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal
- Plasma antithrombin III >= 70%, fibrinogen >= 150 mg/dL, international normalized
ratio (INR) ≤ 1.5, and partial thromboplastin time (PTT) ≤ institutional ULN.
- Total bilirubin ≤ 1.5x institutional ULN
- Patients who have had a stent placed for biliary obstruction can be included in the
study.
- Female subject of childbearing potential must have a negative urine or serum pregnancy
test.
- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.
- Male subjects with a female partner of childbearing potential must agree to use two
adequate methods or a barrier method plus a method of contraception
Exclusion Criteria:
- Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary
adenocarcinoma.
- History of other malignancy ≤ 3 years ago, with the exception of basal cell or
squamous cell carcinoma of the skin, which were treated with local resection only or
carcinoma in situ of the cervix of ductal carcinoma in situ.
- Receiving any other investigational agents 28 days prior to the screening process.
- Patient with evidence of brain metastases. Such patients must be excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to asparaginase, 5FU, oxaliplatin, or irinotecan.
- Any uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection , symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel disease,
any condition that increases the risk of severe irinotecan gastrointestinal toxicity,
or psychiatric illness/social situations that would limit compliance with study
requirements
- Has an active autoimmune disease, or a documented history of autoimmune disease or
syndrome that requires steroids or immunosuppressive agents. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule.
- Has had an allogeneic tissue/solid organ transplant.
- Has received or will receive a live vaccine within 30 days prior to the first
administration of study medication. Seasonal flu vaccines that do not contain live
virus are permitted
- Has known active Hepatitis B or C.
- Patient is pregnant and/or breastfeeding.
- Known to be HIV-positive on combination antiretroviral.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Grade 3 or 4 adverse events |
Time Frame: | 12 months |
Safety Issue: | |
Description: | The number and percentage of all subjects who experience 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. |
Secondary Outcome Measures
Measure: | Objective Response Rate |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Estimated |
Measure: | progression-free survival (PFS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Summarized |
Measure: | overall survival (OS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Summarized |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Georgetown University |
Last Updated
June 14, 2021