Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Georgetown University
• Collaborator: ERYtech Pharma
• Treatments: Fluorouracil; Folfirinox; Irinotecan; Leucovorin; Oxaliplatin

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 >= 65%, 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.