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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01821612
First received: March 25, 2013
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Rate of treatment-related toxicity during preoperative therapy assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Rate of treatment delay (greater than 4 weeks) during preoperative therapy [ Time Frame: Up to 28 weeks ] [ Designated as safety issue: Yes ]
  • Completion rate of all preoperative and operative therapy [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Macroscopic (R0/R1) resection rate defined as number of patients achieved R0 or R1 resection during surgery divided by number of evaluable patients [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Time to locoregional recurrence [ Time Frame: From the date of registration to the date of the first documented locoregional recurrence, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Time to distant recurrence [ Time Frame: From the date of registration to the date of the first documented distant recurrence, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the date of registration to the date of the death due to all causes, assessed up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 irinotecan 180 mg/m^2 IV over 90 minutes on day 1 followed by, leucovorin 400 mg/m^2 IV over 2 hours on day 1 followed by 5-FU 2400 mg/m^2 IV over 46-48 hours).

Two to six weeks following treatment with the mFOLFIRINOX, if the tumor has not spread to other parts of the body then the patient will receive capecitabine 825 mg/m^2, twice daily for 28 days along with radiation therapy. Patients will have surgery within 4-10 weeks of the last dose of chemoradiation if the tumor has gotten smaller or stayed the same.

Within 6-8 weeks following surgery, patients will receive gemcitabine for 2 cycles (1 cycle is 28 days). Gemcitabine will be given IV on days 1, 8 and 15 of every 28 day cycle.

Drug: oxaliplatin
IV
Drug: irinotecan
IV
Drug: leucovorin
IV
Drug: 5-fluorouracil
IV
Drug: capecitabine
PO
Radiation: radiation Procedure: surgery Drug: gemcitabine
IV

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01821612

Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
United States, Kentucky
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States, 70121
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
University Pointe
West Chester, Ohio, United States, 45069
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Matthew Katz, M.D. M.D. Anderson Cancer Center
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01821612     History of Changes
Other Study ID Numbers: A021101  U10CA031946 
Study First Received: March 25, 2013
Last Updated: June 17, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma, Acinar Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Fluorouracil
Capecitabine
Irinotecan
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors

ClinicalTrials.gov processed this record on July 26, 2016