Clinical trial NCT03483038: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Keywords: pancreatic adenocarcinoma
neoadjuvant
ONIVYDE
chemotherapy
borderline resectable
resectable
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2018-03-29
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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-
  1. ANC \> 1,500 cells/μl without the use of hematopoietic growth factors; and
  2. Platelet count \> 100,000 cells/μl; and
  3. Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)

     ii. Hepatic-

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  1. 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),
  2. 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

Primary outcomes:
measure: Percentage of Subjects Who Had Post-operative Complications 30 Days Post-surgery
timeFrame: 30 days
Secondary outcomes:
measure: Percentage of Subjects Who Completed All Intended Cycles of Treatment
timeFrame: 4 months
measure: Percentage of Subjects Who Achieved a Complete Surgical Resection (R0)
timeFrame: 7 months
measure: Percentage of Patients Achieving a Best Overall Response of Partial or Complete Response (Objective Response Rate)
timeFrame: 5 months
measure: Difference Between Baseline and Maximal Nadir of Serum CA19-9 Level
timeFrame: 9 months
measure: Subject Physical, Social, Emotional, and Functional Well-being During Treatment
timeFrame: Cycles 1, 5, and 8 and at pre-surgical evaluation and post-surgical follow-up visits
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Health UF Health Cancer Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Health Care
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
Study officials:
affiliation: University of Florida
name: Thomas George, MD
role: PRINCIPAL_INVESTIGATOR
References: