Folfirinox Or Gemcitabine-Nab Paclitaxel Followed By Stereotactic Body Radiotherapy For Locally Advanced Pancreatic Cancer

Study Overview

Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

This study will implement a new treatment regimen for patients with advanced and inoperable pancreatic cancer using chemotherapy combinations of Folfirinox or gemcitabine-nab paclitaxel (abraxane) followed by a short course of high dose radiation called Stereotactic Body Radiation Therapy (SBRT). While the chemotherapy is standard of care, the strategy of adding SBRT has not been investigated. An increase in the percentage of patients who can proceed to have surgery to remove their disease is anticipated with this approach.

This pilot study will evaluate safety and tolerability of neoadjuvant chemotherapy followed by SBRT. Patients with locally advanced pancreatic cancer (LAPC) and borderline pancreatic inoperable cancer will be assigned to one of two treatment arms based upon performance status and physician's discretion. The two treatment arms are: Folfirinox or gemcitabine-nab paclitaxel (abraxane). There are no study drugs as all treatments are based on standard clinical pathways. After two cycles of treatment patients will be restaged with CT scans or imaging. If the tumor remains resectable, borderline, or unresectable without progression of disease, then the patient will proceed to SBRT. Follow-up visits will continue every three months for up to one year or until progression of disease.

Locally Advanced Pancreatic Cancer
Borderline Pancreatic Inoperable Cancer
Pancreatic Cancer

DRUG: Folfirinox
DRUG: Gemcitabine nab-Paclitaxel

IRB160830003 (UAB 1632)

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 2018-07-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-08-14
First Submitted that Met QC Criteria 2018-07-17	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-08-18
First Posted (ACTUAL) 2018-07-26	Results First Posted N/A	Last Verified 2020-08

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:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Folfirinox + SBRT Folfirinox comprises the following: Fluorouracil 2,400 mg/m2 intravenously over 48 hours Days 1-3 and 15-17 every 4 weeks; Folinic acid 400 mg intravenously on Days 1 and 15 every 4 weeks; Oxaliplatin 85 mg/m2 intravenously on Days 1 and 15 every 4 weeks;	DRUG: Folfirinox SBRT will follow Folfirinox at the completion of Cycle 2 (if eligible).
EXPERIMENTAL: Gemcitabine-nab Paclitaxel + SBRT Gemcitabine-nab Paclitaxel comprises the following: Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 every 4 weeks; nab Paclitaxel 125 mg/m2 on Days 1, 8, and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits	DRUG: Gemcitabine nab-Paclitaxel SBRT will follow Gemcitabine nab-Paclitaxel at the completion of Cycle 2 (if eligible).

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Folfirinox + SBRT

Folfirinox comprises the following: Fluorouracil 2,400 mg/m2 intravenously over 48 hours Days 1-3 and 15-17 every 4 weeks; Folinic acid 400 mg intravenously on Days 1 and 15 every 4 weeks; Oxaliplatin 85 mg/m2 intravenously on Days 1 and 15 every 4 weeks;

DRUG: Folfirinox

SBRT will follow Folfirinox at the completion of Cycle 2 (if eligible).

EXPERIMENTAL: Gemcitabine-nab Paclitaxel + SBRT

Gemcitabine-nab Paclitaxel comprises the following: Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 every 4 weeks; nab Paclitaxel 125 mg/m2 on Days 1, 8, and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits

DRUG: Gemcitabine nab-Paclitaxel

SBRT will follow Gemcitabine nab-Paclitaxel at the completion of Cycle 2 (if eligible).

Primary Outcome Measures	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Initial dose of drug until 4 weeks following completion of therapy which may or may not include SBRT and follow-up. Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.	Baseline up to two years

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	Progression-free survival is the duration of time from study entry to time of disease progression or death, whichever comes first.	Baseline up to two years
Overall survival	Overall survival is the duration of time from study entry to time of death or the date of last contact.	Baseline to two years
Rate of preoperative chemotherapy + radiotherapy completion	The rate will be determined from the measurement of lesions (maximum of 2 per organ with no more than 5 lesions total) from CT scans and magnetic resonance imaging within the study time frame.	Baseline to two years
Proportion of participants undergoing surgery after preoperative chemoradiation therapy	Comparison of participants who underwent surgery versus those that did not following preoperative chemoradiation therapy	Baseline to two years

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:

Histologically or cytologically proven adenocarcinoma of the pancreas. Patients with mixed tumor with predominant adenocarcinoma pathology can be enrolled.
Subjects will be staged according to the 2010 American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-4, being eligible; and have a primary tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)
The tumor must be deemed as being borderline/unresectable. Final CT confirmation of surgical staging/ eligibility will be at the discretion of the pancreatic surgeon of the patient.
Disease must be confined to loco-regional site as confirmed by CT imaging and/or diagnostic staging laparoscopy to avoid occult peritoneal deposits. Diagnostic laparoscopy will be performed only if absolutely required
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on imaging studies CT
Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2.
Age >18
Estimated life expectance >12 weeks
If female patient is of child bearing potential, she must have a negative serum pregnancy test (βhCG) documented up to 72 hrs prior to administration of first study drug
Patient has screening blood work performed which includes the following (should be drawn ≤14 days prior to enrollment)
Absolute neutrophil count (ANC) >1.5 x 109/L
Platelet count ≥100,000/mm3
Hemoglobin (Hgb) ≥ 9g/dL
Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) Total Bilirubin ≤1.5 ULN
Serum Cr within normal limits (WNL)
Prothrombin Time and International Normalized Ratio (PT/INR) and Partial Thromboplastin Time (PTT) within normal limits (±15%).
Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist

Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas
Patients must not have received prior pancreatic surgery, radiation therapy, chemotherapy or any investigational therapy for pancreatic cancer.
Patients with tumors extending or invading duodenum or gastric are not eligible.
Evidence of distant metastasis on upright chest x-ray, CT or other staging studies
Subjects with recurrent disease are not eligible
Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment
Patients with scleroderma, ulcerative colitis or other systemic conditions deemed risky for radiation treatment. Therefore, will be excluded.
Prior chemotherapy
Subjects in their reproductive age who are breast feeding or have a positive pregnancy test
Any co-morbid condition such as but not limited to congestive heart failure, cardiac arrhythmia or psychiatric illness of sufficient severity to limit full compliance with the protocol per assessment by the individual treating physician
Concurrent active infection
No prior malignancy allowed except cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer
Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C
Patient who has undergone recent major surgery, other than diagnostic surgical procedure within 4 weeks prior to enrollment.
Patient who has a history of allergy or hypersensitivity to any of the study drugs.
Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
Patients with greater than grade 2 peripheral neuropathy at the time of enrollment are not eligible.

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Ravi K Paluri, MD, University of Alabama at Birmingham

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

No publications available

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