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
- Conditions
- Pancreatic Adenocarcinoma
- Interventions
- Drug: Liposomal IrinotecanDrug: FOLFOX regimen
- Registration Number
- NCT03483038
- Lead Sponsor
- University of Florida
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 45
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Must be at least 18 years of age.
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A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation
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No clinical evidence of metastatic disease
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Potentially resectable local disease, as confirmed by CT or MRI of the abdomen
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ECOG performance status of 0 or 1
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Any biliary obstruction must have been treated.
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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
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Adequate organ function; as defined by:
i. Hematologic-
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ANC > 1,500 cells/μl without the use of hematopoietic growth factors; and
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Platelet count > 100,000 cells/μl; and
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Hemoglobin > 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
ii. Hepatic-
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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),
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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
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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
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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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Liposomal irinotecan with FOLFOX Liposomal Irinotecan Subjects will receive 8 cycles and each cycle is 14 days. Liposomal irinotecan with FOLFOX FOLFOX regimen Subjects will receive 8 cycles and each cycle is 14 days.
- Primary Outcome Measures
Name Time Method Percentage of Subjects Who Had Post-operative Complications 30 Days Post-surgery 30 days To determine the percentage of subjects who had post-operative complications 30 days post-surgery. Post-operative complications considered for this outcome measure included hospital readmission, death, second surgery or interventional procedure, or major complications extending hospital stay.
- Secondary Outcome Measures
Name Time Method Percentage of Subjects Who Completed All Intended Cycles of Treatment 4 months To determine the percentage of subjects that completed all eight intended cycles of treatment with liposomal irinotecan with FOLFOX.
Percentage of Subjects Who Achieved a Complete Surgical Resection (R0) 7 months To determine the percentage of subjects who achieved a complete surgical resection (R0),which is determined from review of pathology reports and inclusive of pathologic nodal status and TNM staging. A complete surgical resection (R0) has been achieved when surgical margins are microscopically negative for residual tumor.
Percentage of Patients Achieving a Best Overall Response of Partial or Complete Response (Objective Response Rate) 5 months To determine the percentage of patients achieving a best overall response of partial or complete response according to RECIST 1.1 criteria from the start of the treatment until disease progression/recurrence. Per RECIST 1.1 criteria, a complete response is the disappearance of all target lesions (any pathological lymph nodes \[whether target or non-target\] must have reduction in short axis to \<10 mm). A partial response is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Difference Between Baseline and Maximal Nadir of Serum CA19-9 Level 9 months To determine the difference between baseline and maximal nadir of serum CA19-9 level
Subject Physical, Social, Emotional, and Functional Well-being During Treatment Cycles 1, 5, and 8 and at pre-surgical evaluation and post-surgical follow-up visits To determine subject physical, social, emotional, and functional well-being during treatment, as measured by the FACT-G questionnaire. The FACT-G is a 27 item questionnaire where subjects respond to item with a score of 0-4. The responses to the questions are summed to calculate 4 sub-scores: physical well-being (score range 0-28), social well-being (score range: 0-28), emotional well-being (score range: 0-24), and functional well-being (score range: 0-28). The 4 sub-scores are also summed to calculate the total score. Total scores range from 0-108. A higher sub-score or total score indicates better quality of life. Participants completed the FACT-G at Cycles 1, 5, and 8, as well as at the pre-surgical evaluation and follow-up visits.
Trial Locations
- Locations (4)
Orlando Health UF Health Cancer Center
🇺🇸Orlando, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Tallahassee Memorial Health Care
🇺🇸Tallahassee, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States