Borderline Pancreas Study: FOLFIRINOX +SBRT

Study Overview

Primary Objective: To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy. Secondary Objective(s): 1. To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT 2. To investigate the safety and tolerability of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer 3. To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy 4. To assess quality of life through and after treatment using the FACT-Hep questionnaire

The study investigators hypothesize that neoadjuvant FOLFIRINOX can be safely and efficaciously delivered using a sequential regimen with SBRT as an alternative to standard neoadjuvant chemoradiotherapy. Standard of care neoadjuvant treatment typically requires about six weeks of treatment with sub-systemic dosing of chemotherapy. The feasibility of the sequential delivery of the FOLFIRINOX followed by SBRT will be evaluated by capturing the prevalence of grade 3 toxicity and the treatment delay rate. In our study, SBRT is planned sequentially to follow cycle 4 of chemotherapy treatment, provided toxicity has resolved to grade 2 or less. Thus, allowing for resolution of chemotherapy toxicity prior to initiation of radiation therapy. This interval and the fact that there is no concurrent delivery of chemo-RT, based on previously discussed experiences, including approaches where SBRT safely follows other intense chemotherapy regimens (see Polistina et al and Chuong [35,36]) makes this study feasible without establishing toxicity profile. The proposed regimen of 4 cycles of FOLFIRINOX followed by 30 Gy/5 fractions using SBRT will be safely tolerated and will improve resectability rates in borderline resectable PDAC patients. In addition, this regimen will not compromise the ability to achieve a successful Whipple resection. This regimen will improve the local control rate and overall disease free survival in this patient population. The investigators further hypothesize that early administration of FOLFIRNOX will provide optimal systemic therapy to control clinically occult micrometastases.

Resectable Pancreatic Cancer

OTHER: Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable
DRUG: -Oxaliplatin 85 mg/m2 IV on Day 1
DRUG: -Irinotecan 180 mg/m2 IV on Day 1
DRUG: -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours

HP-00055716

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 2013-09-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-08-15
First Submitted that Met QC Criteria 2013-11-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-08-19
First Posted (ACTUAL) 2013-11-25	Results First Posted N/A	Last Verified 2019-08

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
OTHER: Chemotherapy+SBRT prior to surgery if applicable FOLFIRINOX Drugs: * Calcium Folinate (Folinic Acid) 400 mg IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles. Stereotactic Body Radiotherapy (SBRT): 30 Gy in 5 fractions given to radiographically defined pancreatic mass alone	OTHER: Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable Patients will receive chemotherapy (21d/cycle for a total of 4 cycles) plus SBRT before screening for surgical resection of the pancreas. DRUG: -Oxaliplatin 85 mg/m2 IV on Day 1 Oxaliplatin 85 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles). DRUG: -Irinotecan 180 mg/m2 IV on Day 1 Irinotecan 180 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles). DRUG: -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours 5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours of each cycle (21d/cycle for a total of 4 cycles.

Participant Group/Arm

Intervention/Treatment

OTHER: Chemotherapy+SBRT prior to surgery if applicable

FOLFIRINOX Drugs: * Calcium Folinate (Folinic Acid) 400 mg IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles. Stereotactic Body Radiotherapy (SBRT): 30 Gy in 5 fractions given to radiographically defined pancreatic mass alone

OTHER: Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable

Patients will receive chemotherapy (21d/cycle for a total of 4 cycles) plus SBRT before screening for surgical resection of the pancreas.

DRUG: -Oxaliplatin 85 mg/m2 IV on Day 1

Oxaliplatin 85 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).

DRUG: -Irinotecan 180 mg/m2 IV on Day 1

Irinotecan 180 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).

DRUG: -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours

5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours of each cycle (21d/cycle for a total of 4 cycles.

Primary Outcome Measures	Measure Description	Time Frame
Rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy.	To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy (AGGC 6th edition).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.

Secondary Outcome Measures	Measure Description	Time Frame
Survival status (disease-free-survival vs. overall survival) time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT	To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT (RECIST)	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.

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:
18 Years

Accepts Healthy Volunteers:

≥ 18 years at diagnosis.
Biopsy proven pancreatic adenocarcinoma.
Borderline resectable per NCCN criteria (No distant metastases, venous involvement of the portal vein/SMV, demonstrating tumor abutment and narrowing of the lumen, encasement of the portal vein/SMV without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal or distal to this area of vessel involvement, allowing for safe resection and reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; tumor abutment of the SMA not to exceed 180 degrees of the circumference of the vessel wall.).
Radiologically measurable or clinically evaluable disease.
Pancreas protocol CT and/or MRI if required for further clarification of disease tissue planes within 4 weeks of registration.
ECOG PS of 0-2.
Able to get a Whipple resection per surgeon assessment performed within 4 weeks of registration.
The following laboratory values obtained ≤ 28 days prior to registration:
Absolute neutrophil count (ANC) ≥ 1,500/mm3.
Platelet count ≥ 100,000/mm3.
Hemoglobin > 8.0 g/dL.
Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
SGOT (AST) ≤ 2 x ULN.
SGPT (ALT) ≤ 2 x ULN.
Creatinine ≤ 1.5 x ULN.
CA 19-9 level (to establish baseline).
A negative pregnancy test within 7 days prior to registration for women of childbearing potential. In addition, male and female participants must commit to adequate contraception while on study.
Able to provide written informed consent.
Willing to return for all required study assessments.
Neurological assessment for pre-existing peripheral neuropathy.
Documentation of pre-existing hearing deficits.

Any pancreatic adenocarcinoma that does not meet criteria for borderline resectable disease.
Prior history of abdominal radiation therapy.
History of autoimmune disease such as scleroderma, lupus, and inflammatory bowel disease.
Patients with tumor-caused symptomatic bowel obstruction.
Chemotherapy (including hormonal therapy) within the past 5 years from date of registration.
Other invasive malignancies within the past 5 years from date of registration.
Pregnant or nursing women or women of childbearing age that are unwilling to employ adequate contraception.
Other co-morbid conditions which, based on the judgment of the physicians obtaining informed consent, would make the patient inappropriate for this study.

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Shahed Badiyan, MD, University of Maryland, College Park

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

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