Neoadjuvant Folfirinox Followed by Capecitabine and Limited Field Radiation for Localized Pancreatic Head Adenocarcinoma

Study Overview
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Brief Summary
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This study is for subjects with adenocarcinoma of the pancreas. The purpose of this research study is to determine the safety and effectiveness of modified Folfirinox and radiation therapy as treatment for adenocarcinoma (cancer) of the pancreas before surgery. Screening tests will be done to determine if subjects are eligible for participation in this study. If subjects are eligible to participate and agree to participate they will begin chemotherapy. After 3 cycles of chemotherapy, subjects will begin chemoradiation. Within 4 to 8 weeks of completing radiation therapy, subjects will have surgery. There will also be post-treatment and follow-up evaluations. Subjects will be followed for every 3 months for 3 years after their initial registration.

Official Title
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Phase II Study of Neoadjuvant Folfirinox Chemotherapy Followed by Capecitabine With Concurrent Limited Field Radiation Therapy in Patients With Localized Pancreatic Head Adenocarcinoma

Conditions
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Adenocarcinoma of Head of Pancreas

Intervention / Treatment
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* Drug: Neo-adjuvant Chemotherapy
* Radiation: Chemoradiation
* Procedure: Surgical Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has histologically or cytologically confirmed borderline resectable adenocarcinoma of the pancreas. Patients with islet cell or other neuroendocrine neoplasms are excluded. Borderline resectable disease as outlined in the protocol ≥ 18 years of age. Male or non-pregnant and non-lactating female. If a female patient is of childbearing potential, she must have a negative serum pregnancy test (β hCG) documented within 72 hours of the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator. Patient must not have received prior chemotherapy or radiation for pancreatic cancer and no exposure to systemic chemotherapy. Patient have acceptable blood counts, chemistries & coagulation at baseline as outlined in the protocol Patient has an ECOG performance status PS 0-1. Patient has been informed about the nature of the study and has agreed to participate in the study and signed the Informed Consent Form prior to participation in any study-related activities. Endoscopic ultrasound (EUS) with FNA for cytology. Patients should not have any evidence of active or uncontrolled infection requiring treatment with antibiotics. Exclusion Criteria: Patient has localized resectable, locally advanced unresectable or advanced metastatic disease. Patients with adenocarcinoma of the pancreatic body or tail are ineligible. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Patient has known infection with HIV. Patient has undergone major surgery, other than diagnostic surgery (i.e.surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study. Prior chemotherapy, immunotherapy or radiation for pancreatic cancer. Patient has a history of allergy or hypersensitivity to the study drugs. Patient has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive chemotherapy and/or radiation therapy. Patients must not require chronic use of immunosuppressive agents (e.g. methotrexate, cyclosporine). No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years. Patients must not have clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before randomization. Patients must not have a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results. Patient is unwilling or unable to comply with study procedures. Patient is enrolled in any other therapeutic clinical protocol or investigational trial. Patients aged > 70

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Chemotherapy, Chemoradiation, Surgery<br>Neoadjuvant Chemotherapy- Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles for 3 cycles with growth factor support Chemoradiation Surgical Resection | Drug: Neo-adjuvant Chemotherapy<br>* Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles, for three (3) cycles with growth factor support. Restaging # 1. (CT or MRI; use same modality as baseline staging unless otherwise indicated by Study Team) Progressive Disease (PD) → Off study. Subsequent treatment per patient's primary MD. Stable Disease (SD) or Tumor Response → Continue to Registration #2 for Chemoradiation.<br>* Other names: FOLFIRINOX chemotherapy;Radiation: Chemoradiation<br>* Chemoradiation may be administered at selected approved CTN sites. Determination of resectability as reviewed and documented by MUSC-HCC GI Tumor Board. Unresectable → Off study. Subsequent treatment per patient's primary MD. Resectable → Continue to Registration #3 for Surgical Resection<br>Procedure: Surgical Resection<br>* Meets criteria for resectable* →pancreaticoduodenectomy (POD) At time of resection, snap frozen tumor specimen sent for correlative biomarker studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate the R0/R1 Resection Rate | Estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. R0 resection status is macroscopic complete removal of tumor by non-contaminated operation, with neither macroscopic nor microscopic residual tumor. R1 resection status is macroscopic complete removal of tumor by non-contaminated operation, with microscopic residual tumor. | at time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Tumor Response | The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population. | From enrollment to Surgery | 
| Histopathologic Tumor Response | Estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder. | at the time of surgery | 
| Time to Recurrence: | Time to recurrence is defined as the time from surgical resection to disease recurrence or death from any cause. Patients who have not recurred at the end of follow up will have their recurrence time censored at the last date of contact. | 2 years | 
| Overall Survival: | Overall survival is defined as the time from enrollment to death from any cause. Patients still alive at the end of follow up will have their survival time censored at the last date of contact. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NEOADJUVANT FOLFIRINOX CHEMOTHERAPY, LOCALIZED PANCREATIC HEAD ADENOCARCINOMA, RADIATION THERAPY