Chemotherapy And Radiation Therapy Before Surgery Followed By Gemcitabine In Treating Patients With Pancreatic Cancer

Study Overview

Chemotherapy and Radiation Therapy Before Surgery Followed by Gemcitabine in Treating Patients with Pancreatic Cancer

This pilot clinical trial studies combination chemotherapy and radiation therapy before surgery followed by gemcitabine hydrochloride in treating patients with pancreatic cancer. Drugs used in chemotherapy, such as oxaliplatin, irinotecan hydrochloride, leucovorin calcium, fluorouracil, and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

The purpose of this study is to evaluate a new treatment program for patients with borderline resectable pancreas cancer in order to determine what effects, good and bad, chemotherapy and chemoradiation have on your cancer and to see if it allows safe surgery. Primary Objectives: * To assess the accrual rate of this study. * To assess the rate of treatment-related toxicity and treatment delay during preoperative therapy. * To assess the rate of completion of all preoperative and operative therapy. Secondary Objectives: * To assess the macroscopic (R0/R1) resection rate. * To estimate the rate of radiographic and histopathologic response to preoperative therapy. * To estimate the time to locoregional and distant recurrence. * To assess overall survival (OS). * To retrieve nucleic acids from pretreatment pancreatic ductal adenocarcinoma biopsies and to assess the quality of these nucleic acids using a sequencing-based assessment of tumor DNA.

Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer

DRUG: oxaliplatin
DRUG: irinotecan
DRUG: leucovorin
DRUG: 5-fluorouracil
DRUG: capecitabine
RADIATION: radiation
PROCEDURE: surgery
DRUG: gemcitabine

A021101
U10CA031946 (U.S. NIH Grant/Contract)

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 2013-03-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-09
First Submitted that Met QC Criteria 2013-03-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-13
First Posted (ACTUAL) 2013-04-01	Results First Posted N/A	Last Verified 2025-01

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: mFOLFIRINOX, chemoradiation, surgery and gemcitabine Each patient will receive mFOLFIRINOX therapy administered every other week for a total of 4 cycles. Each treatment cycle is a total of 14 days. This treatment program consists of four drugs (oxaliplatin 85 mg/m^2 IV over 2 hours on day 1 followed by irin	DRUG: oxaliplatin IV DRUG: irinotecan IV DRUG: leucovorin IV DRUG: 5-fluorouracil IV DRUG: capecitabine PO RADIATION: radiation PROCEDURE: surgery DRUG: gemcitabine IV

Participant Group/Arm

Intervention/Treatment

OTHER: mFOLFIRINOX, chemoradiation, surgery and gemcitabine

Each patient will receive mFOLFIRINOX therapy administered every other week for a total of 4 cycles. Each treatment cycle is a total of 14 days. This treatment program consists of four drugs (oxaliplatin 85 mg/m^2 IV over 2 hours on day 1 followed by irin

DRUG: oxaliplatin

DRUG: irinotecan

DRUG: leucovorin

DRUG: 5-fluorouracil

DRUG: capecitabine

RADIATION: radiation

PROCEDURE: surgery

DRUG: gemcitabine

Primary Outcome Measures	Measure Description	Time Frame
Accrual rate, calculated by total number of patients accrued divided by number of months from the date the study is opened at the fifth site to the evaluation date		Up to 3 years
Rate of treatment-related toxicity during preoperative therapy assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4		Up to 30 days after completion of study treatment
Rate of treatment delay (greater than 4 weeks) during preoperative therapy		Up to 28 weeks
Completion rate of all preoperative and operative therapy		Up to 30 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Macroscopic (R0/R1) resection rate defined as number of patients achieved R0 or R1 resection during surgery divided by number of evaluable patients		At the time of surgery
Radiographic response rate defined as number of patients who achieved complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during pre-operative therapy divided by the number of evaluable patients		Up to 18 weeks
Histopathologic response rate defined as number of patients who achieved CR or PR determined according to histopathologic examination during pre-operative therapy divided by the number of evaluable patients		Up to 18 weeks
Time to locoregional recurrence		From the date of registration to the date of the first documented locoregional recurrence, assessed up to 3 years
Time to distant recurrence		From the date of registration to the date of the first documented distant recurrence, assessed up to 3 years
Overall survival		From the date of registration to the date of the death due to all causes, assessed up to 3 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:

Documentation of Disease and Radiographic Staging

Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process
Objective radiographic staging with a) contrast-enhanced, helical thin-cut computed tomography (CT)/magnetic resonance imaging (MRI) scan of the abdomen and b) CT scan/MRI of the chest
Note: echoendoscopic staging will be permitted as an adjunctive modality, but all stage definitions below will be determined using CT/MRI as outlined below. In the event echoendoscopic stage and CT/MRI stage are discordant, the CT/MRI stage will be used. Significant discordance should be discussed with the study principal investigator (PI) prior to enrollment
Borderline resectable primary tumor, defined by the presence of any one or more of the following on CT/MRI, and confirmed by central radiographic review:

An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180 degrees of the circumference of the vessel wall
Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
An interface between the tumor and superior mesenteric artery (SMA) measuring < 180 degrees of the circumference of the vessel wall
No potentially resectable disease defined as primary tumors with all of the following:

An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring < 180 degrees of the circumference of the vessel wall
No radiographic interface between the tumor and the (superior mesenteric artery) SMA, hepatic artery or celiac axis
No radiographic evidence of metastatic disease
No metastatic disease defined as any one or more of the following:

Suspicious lymphadenopathy outside the standard surgical field (i.e., aortocaval nodes, distant abdominal nodes)
Radiographic evidence for metastatic disease in distant organs, such as masses in distant organs or ascites
No locally advanced and/or unresectable disease clearly defined by any one or more of the following by CT/MRI:

An interface between the tumor and the SMA measuring ≥ 180 degrees of the circumference of the vessel wall
No interface between the tumor and the aorta
Occlusion of the SMV or portal vein without a sufficient cuff of normal vein above and below the level of obstruction with which to perform venous reconstruction
Long-segment interface (of any degree) between the tumor and the common hepatic artery or its major tributaries with insufficient artery proximal and distal to the interface to perform reconstruction
No prior chemotherapy or chemoradiation for pancreatic cancer
No patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years
Baseline peripheral sensory neuropathy must be grade < 2
No patients with known Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism
No history of pulmonary embolism in the past 6 months
Age ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status 0-1
Pregnancy/Nursing Status: Non-pregnant and non-breast-feeding. Female participants of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic > 12 months to be considered not of childbearing potential.
Required Pre-Registration Laboratory Values:

Granulocytes ≥ 2,000/ul
Hemoglobin > 9 g/dL
Platelets ≥ 100,000/ul
Albumin > 3.0 g/dL
Creatinine ≤1.5 x upper limit of normal (ULN)

Confirmation of pre-registration eligibility criteria as described under "Documentation of Disease and Radiographic Staging" by the Alliance Central Radiographic Review
Required Registration Laboratory Values:

Bilirubin ≤2 mg/dl
AST (SGOT) & ALT (SGPT) ≤ 2.5 x ULN

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Matthew Katz, M.D., M.D. Anderson Cancer Center

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

Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E, Schwartz L, Frankel W, Martin R, Conway W, Truty M, Kindler H, Lowy AM, Bekaii-Saab T, Philip P, Talamonti M, Cardin D, LoConte N, Shen P, Hoffman JP, Venook AP. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg. 2016 Aug 17;151(8):e161137. doi: 10.1001/jamasurg.2016.1137. Epub 2016 Aug 17.

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