Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma

NCT04292743 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: STUDY00002008
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (3)

• Objective Response Rate by RECIST 1.1

  2 years

• Progression-free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

Study Arms (4)

Eryaspase Dose level 0 (75 Units/kg) plus FOLFIRINOX

EXPERIMENTAL

Eryaspase 75 Units/kg will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion). 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.

Biological: Eryaspase; Drug: FOLFIRINOX

Eryaspase Dose level 1 (100 Units/kg) plus FOLFIRINOX

EXPERIMENTAL

Eryaspase 100 Units/kg will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion). 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.

Biological: Eryaspase; Drug: FOLFIRINOX

Eryaspase Dose Level -1 (50 Units/kg) plus FOLFIRINOX

EXPERIMENTAL

Eryaspase 50 Units/kg will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion). 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.

Biological: Eryaspase; Drug: FOLFIRINOX

Eryaspase Dose Level -2 (25 Units/kg) plus FOLFIRINOX

EXPERIMENTAL

Eryaspase 25 Units/kg will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion). 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.

Biological: Eryaspase; Drug: FOLFIRINOX

Interventions

Eryaspase BIOLOGICAL

intravenous administration of Eryaspase, starting dose 75 units/kg, dose escalation to 100 units/kg, dose reduction 50 units/kg and 25 units/kg

Eryaspase Dose Level -1 (50 Units/kg) plus FOLFIRINOX; Eryaspase Dose Level -2 (25 Units/kg) plus FOLFIRINOX; Eryaspase Dose level 0 (75 Units/kg) plus FOLFIRINOX; Eryaspase Dose level 1 (100 Units/kg) plus FOLFIRINOX

FOLFIRINOX DRUG

intravenous administration of FOLFIRINOX

Also known as: 5-fluorouracil, oxaliplatin, Irinotecan, leucovorin

Eryaspase Dose Level -1 (50 Units/kg) plus FOLFIRINOX; Eryaspase Dose Level -2 (25 Units/kg) plus FOLFIRINOX; Eryaspase Dose level 0 (75 Units/kg) plus FOLFIRINOX; Eryaspase Dose level 1 (100 Units/kg) plus FOLFIRINOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \>= 65%, fibrinogen \>= 150 mg/dL, international normalized ratio (INR) ≤ 1.5, and partial thromboplastin time (PTT) ≤ institutional ULN.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Georgetown University: lead
• ERYtech Pharma: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

eryaspase; folfirinox; Fluorouracil; Oxaliplatin; Irinotecan; Leucovorin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Marcus Noel
• Organization: Lombardi Comprehensive Cancer Center

Marcus.S.Noel@gunet.georgetown.edu

202-444-2223

Study Officials

• Marcus S Noel, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose escalation of Eryaspase in combination with FOLFIRINOX

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 3, 2020
• Study Start: December 2, 2020
• Primary Completion: January 18, 2023
• Study Completion: March 4, 2024
• Last Updated: June 11, 2025
• Results First Posted: February 14, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)