A Study of the Safety and Activity of Liposomal Irinotecan in Combination With the 5-FU and Oxaliplatin in the Preoperative Treatment of Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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This is a phase II, single arm, non-randomized, open label study of liposomal irinotecan with FOLFOX in the neoadjuvant setting in patients with resectable or borderline resectable, previously untreated pancreatic adenocarcinoma. The primary objective of this study is to investigate the safety and feasibility of this treatment regimen in this patient population.

Official Title
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A Phase II, Open-label Pilot Study Evaluating the Safety and Activity of Liposomal Irinotecan in Combination With 5-FU and Oxaliplatin in Preoperative Treatment of Pancreatic Adenocarcinoma (NEO-Nal- IRI Study)

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Liposomal Irinotecan
* Drug: FOLFOX regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be at least 18 years of age. A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation No clinical evidence of metastatic disease Potentially resectable local disease, as confirmed by CT or MRI of the abdomen ECOG performance status of 0 or 1 Any biliary obstruction must have been treated. Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1*28 with results available to study team prior to treatment initiation Adequate organ function; as defined by: i. Hematologic- ANC > 1,500 cells/μl without the use of hematopoietic growth factors; and Platelet count > 100,000 cells/μl; and Hemoglobin > 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL) ii. Hepatic- Serum total bilirubin within 1.5 x upper limit of normal (ULN) for the institution, with a trend downwards (biliary drainage is allowed for biliary obstruction), AST and ALT less than or equal to 2.5 x ULN iii. Renal- Serum creatinine less than or equal to 1.5 x ULN iv. Cardiac- Normal ECG or ECG without any clinically significant findings as defined by the treating physician Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 7 months after the last dose of study drug to minimize the risk of pregnancy Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug. Exclusion Criteria: A medical history of prior anti-cancer treatment for pancreatic cancer. Locally advanced unresectable disease or evidence of metastatic disease. Any other invasive malignancy within the past three years. Presence of any known contraindications to or hypersensitivities to the investigational products. Use of strong CYP3A4 inhibitors or inducers which cannot be discontinued prior to study entry. A non-surgical candidate. Subject is unable to understand, provide consent or comply with study requirements, treatments or instructions in the opinion of the treating physician. Uncontrolled diarrhea, active infection, known interstitial lung disease or other medical condition that precludes safe administration of this combination therapy consistent with manufacturer recommendations. Unwilling/unable to comply with birth control requirements while on study. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 7 months for females and 4 months for males after the last dose of study drug. Females who are pregnant or breastfeeding. History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. Prisoners or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness. Subjects demonstrating an inability to comply with the study and/or follow-up procedures. Known dihydrypyrimidine (DPD) deficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposomal irinotecan with FOLFOX<br>Subjects will receive 8 cycles and each cycle is 14 days. | Drug: Liposomal Irinotecan<br>* Subjects will receive 60 mg/m2 intravenously on Day 1 of each 14 day cycle.<br>* Other names: ONIVYDE;Drug: FOLFOX regimen<br>* Subjects will receive FOLFOX (oxaliplatin 60 mg/m2 IV, leucovorin 400 mg/m2 IV, and 5-fluorouracil 2400 mg/m2 IV) on Day 1 of each 14 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30 day post operative complication rate | To determine the 30 day post operative complication rate, as measured by hospital readmission, death, second surgery or interventional procedure, or major complications extending hospital stay | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Completion Rate | To determine the treatment completion rate of therapy, as defined by the percentage of subjects that completed all intended cycles | 4 months | 
| Rate of complete surgical resection | To determine the rate of complete surgical resection (R0) | 7 months | 
| Objective Response Rate | To determine radiographic objective response rate of the primary tumor as measured by RECIST v 1.1 criteria | 5 months | 
| Biochemical Response Rate | To determine the biochemical response rate and pattern of response as measured by serial CA 19-9 levels | 9 months | 
| Patient-Reported Quality of Life | To determine the patient-reported quality of life during treatment as measured by the NCI validated FACT-G survey | 9 months | 
| Rate of other pathologic downstaging | To determine the rate of other pathologic downstaging | 7 months | 
| To determine the safety of liposomal irinotecan in combination with 5-fluorouracil, oxaliplatin, and leucovorin as assessed by the number of treatment-related adverse events as assessed by CTCAE v 4.0 |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic adenocarcinoma, neoadjuvant, ONIVYDE, chemotherapy, borderline resectable, resectable