Clinical Trials /

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma

NCT04292743

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).

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
EryaspaseEryaspase plus FOLFIRINOX
FOLFIRINOX5-fluorouracil, oxaliplatin, Irinotecan, leucovorinEryaspase 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

NameTypeDescriptionInterventions
Eryaspase plus FOLFIRINOXExperimentalEryaspase 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.
  • Eryaspase
  • FOLFIRINOX

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 >=60
                  mL/min/1.73 m2 for patients with creatinine levels above institutional normal
                  (using the Cockcroft-Gault formula)

               -  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:

          -  Patient must not have evidence of neuroendocrine tumor, duodenal adenocarcinoma, or
             ampullary adenocarcinoma.

          -  Patient must not have a 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.

          -  Patient must not be receiving any other investigational agents 28 days prior to the
             screening process.

          -  Patient must not have 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.

          -  Patient must not have a history of allergic reactions attributed to compounds of
             similar chemical or biologic composition to asparaginase, 5FU, oxaliplatin, or
             irinotecan.

          -  Patient must not have an 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 must not be pregnant and/or breastfeeding.

          -  Patient must not be 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

December 10, 2020