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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01821612
First received: March 25, 2013
Last updated: June 5, 2013
Last verified: April 2013
  Purpose

This pilot clinical trial studies combination chemotherapy and radiation therapy before surgery followed by gemcitabine hydrochloride in treating patients with pancreatic cancer when the tumor is borderline for removal. 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 together with 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 hydrochloride
Drug: leucovorin calcium
Drug: 5-fluorouracil
Drug: capecitabine
Radiation: radiation
Procedure: surgery
Drug: gemcitabine hydrochloride

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 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mFOLFIRINOX, chemoradiation, surgery and gemcitabine
Patients receive mFOLFIRINOX chemotherapy comprised of oxaliplatin, irinotecan hydrochloride, leucovorin calcium and 5-fluorouracil. After completion of chemotherapy, patients receive chemoradiation comprised of capecitabine and radiation then undergo surgery. After completion of surgery, patients receive gemcitabine hydrochloride.
Drug: oxaliplatin
Patients receive 85 mg/m2 intravenously (IV) over 2 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Patients receive irinotecan hydrochloride intravenously (IV) 180 mg/m2 over 90 minutes on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: leucovorin calcium
Patients receive leucovorin calcium 400 mg/m2 intravenously (IV) over 2 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Other Names:
  • folinic acid
  • calcium folinate
  • citrovorum factor
  • N 5-formyltetrahydrofolate
  • 5-formyl-FH4
Drug: 5-fluorouracil
Patients receive 5-fluorouracil 2,400 mg/m2 intravenously (IV) over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine
Patients receive capecitabine 825mg/m2 orally (PO) twice daily (BID) 5 days a week for 4 weeks.
Other Names:
  • Xeloda
  • 5'-deoxy-5fluoro-N-[(pentyloxy)carbonyl]-cytidine)
Radiation: radiation
Patients will receive radiation therapy 5 days a week for 4 weeks.
Procedure: surgery
Patients undergo pancreaticoduodenectomy within 4-10 weeks of completing chemoradiation.
Drug: gemcitabine hydrochloride
Patients receive gemicitabine hydrochloride intravenously (IV) 1000 mg/m2 over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Other Names:
  • 2'deoxy-2'
  • 2'-difluorocytidine
  • dFDC
  • difluorodeoxycytidine
  • gemcitabine
  • Gemzar

Detailed Description:

Patients receive mFOLFIRINOX chemotherapy comprising oxaliplatin intravenously 85 mg/m2 (IV) over 2 hours on day 1, irinotecan 180 mg/m2 IV over 90 minutes on day 1, leucovorin calcium 400 mg/m2 IV over 2 hours on day 1, and 5-fluorouracil 2,400 mg/m2 IV over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Beginning 2-6 weeks after completion of therapy, patients receive capecitabine 825 mg/m2 orally (PO) twice daily (BID) 5 days a week and undergo radiation therapy 5 days a week for 4 weeks. Patients undergo surgery within 4-10 weeks of completing radiation.Beginning 6-8 weeks after surgery, patients receive gemcitabine IV IV 1000 mg/m2 on days 1, 8, and 15 over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 months for 3 years and then periodically thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
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)
    • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase [SGOT] & alanine aminotransferase (ALT) serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x 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
    • Cancer antigen (CA)19-9 < 1000 U/ml (from time point when bilirubin is ≤ 2 mg/dl)
  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, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: W. Charles Conway    504-842-4482      
Principal Investigator: W. Charles Conway         
United States, Tennessee
Vanderbilt University/Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Dana Cardin    615-322-4967      
Principal Investigator: Dana Cardin         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Matthew Katz    713-745-1462      
Principal Investigator: Matthew Katz         
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Matthew Katz, M.D. M.D. Anderson Cancer Center
  More Information

No publications provided

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 5, 2013
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
Capecitabine
Fluorouracil
Irinotecan
Camptothecin
Oxaliplatin
Calcium, Dietary
Levoleucovorin
Leucovorin
Formyltetrahydrofolates
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents

ClinicalTrials.gov processed this record on September 18, 2014