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

Stage III Pancreatic Cancer Clinical Trial

Official title:

Neoadjuvant FOLFIRINOX and Chemoradiation Followed by Definitive Surgery and Postoperative Gemcitabine for Patients With Borderline Resectable Pancreatic Adenocarcinoma: An Intergroup Single-Arm Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01821612
• Other study ID #: A021101
• Secondary ID: U10CA031946
• Status: Completed
• Phase: Early Phase 1
• Start date: May 2013
• Est. completion date: June 15, 2018

Study information

• Verified date: August 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 15, 2018
• Est. primary completion date: September 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Pre-Registration Eligibility Criteria

• 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)

Registration Eligibility Criteria

• 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• oxaliplatin
IV
• irinotecan
IV
• leucovorin
IV
• 5-fluorouracil
IV
• capecitabine
PO

Radiation:
• radiation

Procedure:
• surgery

Drug:
• gemcitabine
IV

Locations

Country	Name	City	State
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	M D Anderson Cancer Center	Houston	Texas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University Pointe	West Chester	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Rate of treatment delay (greater than 4 weeks) during preoperative therapy		Up to 28 weeks
Primary	Completion rate of all preoperative and operative therapy		Up to 30 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to locoregional recurrence		From the date of registration to the date of the first documented locoregional recurrence, assessed up to 3 years
Secondary	Time to distant recurrence		From the date of registration to the date of the first documented distant recurrence, assessed up to 3 years
Secondary	Overall survival		From the date of registration to the date of the death due to all causes, assessed up to 3 years