Phase I Study Of Stereotactic Body Radiation Therapy And FOLFIRINOX In The Neoadjuvant Therapy Of Pancreatic Cancer

Study Overview

Phase I Study of Stereotactic Body Radiation Therapy and FOLFIRINOX in the Neoadjuvant Therapy of Pancreatic Cancer

The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. This study will obtain preliminary data on the response of the cancer to this therapy by Magnetic Resonance Imaging (MRI) and by studying the cancer after it is resected surgically. In addition, the investigators will perform biochemical studies on the tumor tissue obtained from your tissue biopsy as well as from the tumor removed by the surgeon in order to measure the effect of treatment with FOLFIRINOX and SBRT on several proteins that may be important in the behavior of pancreatic cancer cells. The data obtained from this trial will be extremely valuable to help improve the approach to treating pancreatic cancer in the future. If you do not undergo surgery after completion of FOLFIRINOX + SBRT, the investigators will request a second biopsy of the tumor under computer tomography (CT) -guidance in order to measure the effect of treatment on your tumor.

The current standard of care for treating early stage pancreatic cancer involves surgery followed by chemotherapy and / or chemoradiotherapy using conventional fractionated external beam radiation therapy (EBRT). Despite the the incorporation of multi-modality adjuvant therapy following surgery, patients with surgically resected pancreas cancer have a high likelihood of recurrence of their cancer and/ or death from their disease. Patients with more advanced pancreatic cancers experience even worse outcomes in the face of unresectable disease or lower likelihood of achieving a negative margin resection. In these particular group of patients, chemotherapy and radiation given prior to surgery may help select patients who are more likely ultimately to benefit from a pancreaticoduodenectomy and may improve the rate of margin negative resection, factors which may influence their outcome. Systemic chemotherapy traditionally used in the treatment of pancreatic cancer has included drugs such as gemcitabine or 5-fluorouracil (5-FU). Recently, a multi-agent chemotherapy regimen called FOLFIRINOX has shown significant efficacy in patients with advanced pancreatic cancer with improved tumor responses and improved overall outcomes with a reasonable toxicity profile. Stereotactic body radiotherapy (SBRT) is a unique radiation technique that allows higher doses of radiation to be delivered to the cancer over a significantly shorter period of time compared to conventional radiation. SBRT's advantages over conventional radiation include: shorter duration of therapy (one to three days versus two to five weeks) as well as the ability to deliver full doses of chemotherapy. In treating patients with pancreatic cancer, SBRT has been tolerated and has been effective when compared historically to conventional radiation. SBRT has been combined with chemotherapy and has also been very well tolerated in patients with pancreatic cancer. This study will ask whether giving chemotherapy with FOLFIRINOX followed in short sequence by radiation therapy using Stereotactic Body Radiation Therapy (SBRT) is safe and feasible. This study will also begin to ask what is the effect of this approach on the rate of margin negative resection in patients who may subsequently undergo surgery for their pancreatic cancer.

Cancer of Pancreas
Cancer of the Pancreas
Neoplasms, Pancreatic
Pancreas Cancer
Pancreas Neoplasms

DRUG: Modified FOLFIRINOX
RADIATION: Stereotactic Body Radiotherapy (SBRT)

IRB00051215
WCI1998-11 (OTHER Identifier) (OTHER: Other)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-09-26	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2016-03-21
First Submitted that Met QC Criteria 2011-10-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2016-03-22
First Posted (ESTIMATED) 2011-10-05	Results First Posted N/A	Last Verified 2016-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 5-Fluorouracil, Oxaliplatin, Irinotecan 5-Fluorouracil, Oxaliplatin, Irinotecan are administered as a modified FOLFIRINOX regimen every 15 days. Subjects receive bi-weekly cycles of therapy on the 1st week, the 3rd week, the 5th week and finally the 7th week for a total of 4 cycles. Assessments	DRUG: Modified FOLFIRINOX Patients receive modified FOLFIRINOX Chemotherapy for 4 cycles (1 cycle = 15 days). Modified FOLFIRINOX: Oxaliplatin 85 mg/m2 intravenous infusion on day 1; Irinotecan 180 mg/m2 intravenous infusion on day 1; 5-Fluorouracil 2400 mg/m2 continuous intraveno RADIATION: Stereotactic Body Radiotherapy (SBRT) Patients will receive Stereotactic Body Radiotherapy (SBRT) to pancreas tumor 2 weeks following chemotherapy. SBRT is given in 3 daily fractions at designated doses per treatment cohort. Starting dose level-Dose level 1: 10 Gy SBRT to primary tumor volume

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 5-Fluorouracil, Oxaliplatin, Irinotecan

5-Fluorouracil, Oxaliplatin, Irinotecan are administered as a modified FOLFIRINOX regimen every 15 days. Subjects receive bi-weekly cycles of therapy on the 1st week, the 3rd week, the 5th week and finally the 7th week for a total of 4 cycles. Assessments

DRUG: Modified FOLFIRINOX

Patients receive modified FOLFIRINOX Chemotherapy for 4 cycles (1 cycle = 15 days). Modified FOLFIRINOX: Oxaliplatin 85 mg/m2 intravenous infusion on day 1; Irinotecan 180 mg/m2 intravenous infusion on day 1; 5-Fluorouracil 2400 mg/m2 continuous intraveno

RADIATION: Stereotactic Body Radiotherapy (SBRT)

Patients will receive Stereotactic Body Radiotherapy (SBRT) to pancreas tumor 2 weeks following chemotherapy. SBRT is given in 3 daily fractions at designated doses per treatment cohort. Starting dose level-Dose level 1: 10 Gy SBRT to primary tumor volume

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated total dose of stereotactic body radiation to patients with resectable or borderline resectable pancreas cancer following FOLFIRINOX chemotherapy	A standard 3 + 3 design will be used for evaluating the safety and tolerability of SBRT radiation doses. Any grade 3 liver, gastric, small bowel or spinal cord toxicity or any grade 4 toxicity (hematologic or other non-hematologic except for diarrhea) will be considered a dose limiting toxicity (DLT). Each cohort will consist of 3 patients, unless 1 of the patients experiences a DLT in which case the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will be defined as the dose level below that which results in a DLT in 2 or more of the 6 patients in a cohort.	Four weeks

Secondary Outcome Measures	Measure Description	Time Frame
Clinical and pathologic objective response rate as measured by MRI (clinical response) and histopathology and rate of complete resection (R0) (pathologic response)	The overall pathologic (complete + partial) response rate and margin negative resection rate will be estimated using all registered patients and all resected patients (via the Intention to Treat principle for effectiveness assessment). The overall objective clinical response rate will involve MRI assessment of pancreas tumors of all registered patients with comparison of baseline (pre-treatment) MRI measurement to post-treatment MRI measurement prior to surgical resection using the Response Evaluation Criteria in Solid Tumors (RECIST). Measurements will involve all registered patients.	ten weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
21 Years

Accepts Healthy Volunteers:

Histologic or cytologic diagnosis of pancreatic adenocarcinoma.
Radiographically resectable or borderline resectable disease as reviewed by an experienced surgical oncologist at Emory.
Age 21 years or older.
Not received prior chemotherapy or radiation for pancreatic cancer.
ECOG performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Adequate bone marrow function: absolute neutrophil count > 1,500/cmm, platelet count > 100,000/cmm.
Understanding and be informed of the investigational nature of this study and must give written informed consent prior to the receiving of treatment per this protocol.

Histologies including endocrine tumors or lymphoma of the pancreas.
A tumor which is less than 3 mm from the duodenum as measured by either CT or MRI.
History of central nervous system (CNS) metastases.
Liver dysfunction, including total bilirubin > 1.5 mg/dL; aspartate transaminase (AST) and alanine amino transferase (ALT) > 5 times upper limit of the institutional normal.
Creatinine ≥ 1.5 mg/dL.
Albumin ≤ 2.5 g/dL.
International Normalized Ratio (INR) ≥ 1.5 (in the absence of ongoing treatment with warfarin).
Breast feeding.
Serious active infection.
Serious concurrent systemic disorders incompatible with participating in the study (at the discretion of the investigator).
An active second primary malignancy (except in situ carcinoma of the cervix, or adequately treated basal cell carcinoma of the skin) within less than one year of enrollment into this study.
Clinical evidence of distant metastatic disease.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Natalyn N. Hawk, MD, PhD, Emory University Winship Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Shaib WL, Hawk N, Cassidy RJ, Chen Z, Zhang C, Brutcher E, Kooby D, Maithel SK, Sarmiento JM, Landry J, El-Rayes BF. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458). Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):296-303. doi: 10.1016/j.ijrobp.2016.05.010. Epub 2016 May 24.

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