Neoadjuvant Modified FOLFIRINOX in Borderline Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Detailed Description
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Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The 5-year survival rate in overall patients is less than 6% due to late clinical manifestation and the systemic nature of the disease at presentation. Even in patients with resectable disease, estimated 5-year survival rates after resection are between 15% and 20%. Traditionally, resection alone is regarded as inadequate for cure. Therefore, systemic and/or combined chemotherapy and radiotherapy have been used as preoperative or postoperative therapy. Neoadjuvant treatment offers several theoretical advantages over an initial resection. Early delivery of systemic therapy for all patients which might lead to the higher rates of negative margin resection rate, and enhanced patient selection for surgery. Although neoadjuvant treatment has been established as a standard of care for resectable or locally advanced disease of breast, gastric, and rectal cancers, the role of neoadjuvant treatment in patients with pancreatic cancer is not clear at present. There is no global consensus on the management of patients with borderline resectable pancreatic cancer. If initially resected, postoperative adjuvant chemotherapy or chemoradiotherapy is standard. However, there is no standard regimen for neoadjuvant chemotherapy for pancreatic cancer. Recent pivotal phase 2/3 trial has demonstrated that FOLFIRINOX improved the response rates and survival outcomes of patients with metastatic pancreatic cancer compared to gemcitabine. Because of higher response rates (about 30%) with FOLFIRINOX, this regimen is now widely investigated in the neoadjuvant setting. Therefore, investigators hypothesize that neoadjuvant FOLFIRINOX may enhance the outcomes of patients with borderline resectable pancreatic cancer. This study will assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Official Title
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Phase 2 Study of Neoadjuvant Modified FOLFIRINOX in Patients With Borderline Resectable Pancreas Adenocarcinoma

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 19 years and older Cytologically or histologically confirmed adenocarcinoma of the pancreas Met the NCCN criteria for borderline resectable disease (assessed at Aug 23rd, 2015) No previous chemotherapy or radiotherapy Eastern Cooperative Oncology Group (ECOG) performance status 0   1 Adequate bone marrow function as defined by platelets ≥ 100 x 109/L and neutrophils ≥ 1.5 x 109/L Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN) Adequate hepatic function with serum total bilirubin < 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent > 5 years previously without evidence of relapse Written informed consent to the study Exclusion Criteria: No potentially resectable disease or no metastatic disease Locally advanced unresectable disease according to the NCCN criteria Histologically confirmed adenosquamous carcinoma Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy Obstruction of gastrointestinal tract Active gastrointestinal bleeding Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.

Ages Eligible for Study
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Minimum Age: 19 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: Perioperative chemotherapy<br>Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Postoperative gemcitabine, every 4 weeks, 3-6 cycles | Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine<br>* Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Oxaliplatin IV 85 mg/m2 Day (D) 1 Irinotecan IV 180 mg/m2 D1 5-FU continuous IV infusion 2,400 mg/m2 over 46 hours D1-2 Leucovorin IV 400 mg/m2 D1 Postoperative gemcitabine, every 4 weeks, 3-6 cycles - Gemcitabine 1,000 mg/ m2 D1, 8, and 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year progression-free survival (PFS) rate | PFS rate at 1 year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Median PFS | 3 years | 
| Overall survival (OS) | Median OS | 3 years | 
| Macroscopic complete resection rate | The rate of no gross residual disease after surgery | 5 months | 
| Response rate | Response rate defined by Response Evaluation Criteria in Solid Tumor version 1.1 | 4 months | 
| Toxicity profile | Adverse events graded by National Cancer Institute Common Terminology Criteria version 4.03 | 1 year | 
| Biomarker analysis | Blood-based biomarker analysis for the correlation with response rate, progression-free survival and overall survival | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic adenocarcinoma, Borderline resectable, Neoadjuvant chemotherapy, FOLFIRINOX