Phase II Study of Preoperative FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel in Patients With Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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This research study is a Phase II clinical trial, which evaluates a combination of drugs, FOLFIRINOX and Gemcitabine/Nab-Paclitaxel, in the management of participants with resectable pancreatic cancer prior to surgery.

Detailed Description
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Patients who fulfill eligibility criteria will be randomized to Arm A or Arm B Treatment will be administered on an outpatient basis. Upon registration participants will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel). After completion of FOLFIRINOX or Gemcitabine/Nab-paclitaxel, all participants without progressive disease will proceed to radiation therapy with capecitabine . Between 2 and 4 weeks after radiation is complete, participants will proceed for surgical resection of pancreatic cancer

Official Title
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Phase II Study of Preoperative FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel in Patients With Resectable Pancreatic Cancer

Conditions
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Resectable Pancreatic Cancer, Pancreatic Ductal Carcinoma

Intervention / Treatment
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* Drug: FOLFIRINOX
* Drug: Gemcitabine/nab-Paclitaxel
* Radiation: Radiation therapy
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to study entry. No evidence of metastatic disease as determined by chest CT scan, and abdominal CT scan (or MRI with gadolinium and/or manganese) and laparoscopy. All patients must be staged with a physical exam, chest CT, abdominal CT with intravenous contrast (or abdominal MRI with gadolinium and/or manganese). Only potentially resectable patients are eligible. Potentially resectable is defined as a) no extrapancreatic disease, b) no evidence (on CT) of involvement of the celiac axis or SMA, c) no evidence (CT or MRI) of occlusion of the SMV or SMPV confluence, and d) no evidence of gross peritoneal or distant metastases by laparoscopy. Patients must be 18 years old or older. There will be no upper age restriction. ECOG Performance Status of 0 or 1 are eligible. Life expectancy of greater than 3 months. Lab Values: ANC ≥ 1500 cells/mm3 Platelet count at least 100,000 cells/mm3. AST and ALT ≤2.5 x upper limit of normal Total Bilirubin ≤ 5 x upper limit of normal if patient is s/p biliary stenting AND decreasing at least two time points after stenting. Total Bilirubin ≤ 1.5 x upper limit of normal if no biliary stenting was done Serum Creatinine ≤1.5mg/dl OR Creatinine Clearance greater than or equal to 30ml/min (as estimated by Cockroft Gault Equation) (140 - age [yrs]) (body wt [kg]) Creatinine clearance for males = ------------ (72) (serum creatinine [mg/dL]) Creatinine clearance for females = 0.85 x male value The effects of radiation on the developing human fetus are known to be teratogenic. Women of child-bearing 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 treatment plus 30 days from the last date of study drug administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who fulfill any of the following criteria will be excluded: The presence of metastatic disease on imaging or laparoscopy. Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by fever. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor. Diagnosis for other invasive carcinomas (except basal cell carcinoma/squamous cell carcinoma of the skin) within the last five years. Carcinoma in-situ is allowed. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation. Unwillingness to participate or inability to comply with the protocol for the duration of the study. Participation in any investigational drug study within 4 weeks preceding the start of study treatment. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake. Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folfirinox-ARM A<br>Upon registration patients will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel Treatment will be administered on an outpatient basis and will include intravenous administration of the FOLFIRINOX regimen on predetermined days. After completion of FOLFIRINOX all patients without progressive disease will proceed with radiation therapy with the standard dose of capecitabine. Between 2 and 4 weeks after radiation is complete, patients will proceed for surgical resection of pancreatic cancer | Drug: FOLFIRINOX<br> <br> Radiation: Radiation therapy<br> <br> Drug: Capecitabine<br> <br> * Other names: Xeloda;|
| Experimental: Gemcitabine/nab-Paclitaxel- Arm B<br>Treatment will be administered on an outpatient basis. Upon registration patients will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel). Intravenous administration of the Gemcitabine/Nab-paclitaxel regimen on predetermined days of each 28 day treatment cycle (unless a delay is mandated by toxicity criteria). A cycle of Gemcitabine/Nab-paclitaxel will constitute a 28 day treatment period. After Gemcitabine/Nab-paclitaxel, all patients without progressive disease will proceed to radiation therapy with the standard dose of capecitabine Between 2 and 4 weeks after radiation is complete, patients will proceed for surgical resection of pancreatic cancer | Drug: Gemcitabine/nab-Paclitaxel<br> <br> Radiation: Radiation therapy<br> <br> Drug: Capecitabine<br> <br> * Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Rate at 18 Month | Number of participants surviving after 18 months of study follow-up | 18 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate (pCR). | Number of patients achieving pathologic complete response at 18 months. Pathologic complete response is defined as the absence of residual invasive disease in the panaceas and in the regional lymph nodes. | 18 Months | 
| Overall Survival Rate | Overall survival rate at five years using Kaplan-Meier survival analysis | Baseline, 5 Years | 
| Number of Participants With Serious and Non-Serious Adverse Events | Number of Participants with Serious and Non-Serious Adverse Events from baseline to 28 days | Baseline, 28 Days | 
| Surgical Morbidity Rate | Number of patients experiencing a specific surgery related morbidity | within 30 days of surgery | 
| 30-day Post-operative Mortality Rate | Number of patients who died following surgery. | 30 Days | 
| Correlation of Biomarkers With PFS | Analysis of the correlation between selected bio-markers and progression free survival. | 2 Years | 
| Rate of Pathologic Downstaging | The number of participants achieving a reduction in the pathological staging of the primary cancer. | 2 Years | 
| Local Control Rate | The number of participants achieving local control. The local control rate is defined as the number of participants achieving stable disease, partial response, or a complete response. | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable pancreatic cancer, Pancreatic Ductal Carcinoma