Phase I Study of Stereotactic Body Radiation Therapy and FOLFIRINOX in the Neoadjuvant Therapy of Pancreatic Cancer
2 other identifiers
interventional
13
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2011
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2011
CompletedFirst Posted
Study publicly available on registry
October 5, 2011
CompletedStudy Start
First participant enrolled
November 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2015
CompletedMarch 22, 2016
March 1, 2016
3.3 years
September 26, 2011
March 21, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Clinical and pathologic objective response rate as measured by MRI (clinical response) and histopathology and rate of complete resection (R0) (pathologic response)
ten weeks
Study Arms (1)
5-Fluorouracil, Oxaliplatin, Irinotecan
EXPERIMENTAL5-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 include history and physical, laboratory tests on a weekly basis throughout the treatment period prior to and including week 8 assessment for stereotactic body radiotherapy (SBRT).
Interventions
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 intravenous infusion on days 1 to 3; pegylated filgrastim (neulasta) 6 mg subcutaneous injection on day 3.
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 (PTV) / 2 Gy SBRT to the retroperitoneal margin daily for a total Gy to Gross tumor volume (GTV) of 36 Gy. There are weekly toxicity assessments for 4 weeks. This is a standard 3 + 3 design with 4 dose levels.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Emory Universitylead
Study Sites (2)
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Related Publications (1)
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.
PMID: 27475674DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Natalyn N. Hawk, MD, PhD
Emory University Winship Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 26, 2011
First Posted
October 5, 2011
Study Start
November 1, 2011
Primary Completion
March 1, 2015
Study Completion
March 1, 2015
Last Updated
March 22, 2016
Record last verified: 2016-03