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Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer

NCT02839343

Description:

This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer
  • Official Title: Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas

Clinical Trial IDs

  • ORG STUDY ID: A021501
  • SECONDARY ID: NCI-2016-00456
  • NCT ID: NCT02839343

Conditions

  • Pancreatic Adenocarcinoma
  • Borderline Resectable Adenocarcinoma of the Head of the Pancrease

Interventions

DrugSynonymsArms
mFOLFIRINOXmFOLFIRINOX + surgery + FOLFOX
FOLFOXmFOLFIRINOX + surgery + FOLFOX

Purpose

The purpose of this study is to compare any good and bad effects of using chemotherapy compared to chemotherapy and radiation prior to surgery. This study will allow the researchers to know whether which approach is better, the same, or worse than the other.

Detailed Description

      This is a randomized phase II study to evaluate 18-month overall survival rate in patients
      with borderline resectable cancer of the head of the pancreas using one of the treatment
      regimens. Eastern Cooperative Oncology Group Performance Status 0 vs 1 is a stratification
      factor. The primary and secondary objectives are described below.

      Primary Objective:

      To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline
      resectable PDAC receiving neoadjuvant therapy consisting of one of the following regimens
      prior to intended surgical resection and adjuvant therapy with 4 cycles of FOLFOX:

        1. Arm 1: 8 cycles of systemic FOLFIRINOX, and/or

        2. Arm 2: 7 cycles of systemic FOLFIRINOX followed by hypofractionated radiation therapy

      Secondary Objectives:

        1. To evaluate and estimate the R0 resection rates in patients receiving each of the two
           multimodality treatment regimens.

        2. To evaluate and estimate the event-free survival in patients receiving each of the two
           multimodality treatment regimens.

        3. To evaluate and estimate the pathologic compete response (pCR) rates in patients
           receiving each of the two multimodality treatment regimens

        4. To assess the adverse events (AE) profile and safety of each treatment arm.

      Patients will be followed up to 5 years post-registration.
    

Trial Arms

NameTypeDescriptionInterventions
mFOLFIRINOX + surgery + FOLFOXExperimentalPatients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
  • mFOLFIRINOX
  • FOLFOX
mFOLFIRINOX + radiation + surgery + FOLFOXExperimentalPatients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
  • mFOLFIRINOX
  • FOLFOX

Eligibility Criteria

        Pre-Registration Eligibility Criteria:

          1. Documentation of Disease:

               -  Pathology: Cytologic or histologic proof of adenocarcinoma of the pancreatic
                  head or uncinate process. Diagnosis should be verified by local pathologist.

               -  TNM Stage: TX, T1-4N0-1orNxM0*

                    -  M1 disease includes spread to distant lymph nodes, organs, and ascites

               -  Criteria for borderline resectable disease: Local radiographic reading must be
                  consistent with borderline resectable cancer of the pancreatic head as defined
                  by intergroup radiographic criteria and must meet any one or more of the
                  following on CT/MRI:

                    -  An interface is present between the primary tumor and the superior
                       mesenteric vein or portal vein and measures ≥ 180° of the circumference of
                       the vessel wall

                    -  Short-segment occlusion of the SMV-PV is present with normal vein above and
                       below the level of obstruction that is amenable to resection and venous
                       reconstruction

                    -  Short segment interface (of any degree) is present between tumor and
                       hepatic artery with normal artery proximal and distal to the interface that
                       is amenable to resection and reconstruction

                    -  An interface is present between the tumor and superior mesenteric artery or
                       celiac axis measuring < 180° of the circumference of the vessel wall

               -  Patients with less extensive disease than the above four (4) criteria are
                  considered potentially resectable and are NOT eligible.

               -  Patients with more extensive disease than the above 4 criteria are considered
                  locally advanced and are NOT eligible.

               -  In addition patients with the following are considered locally advanced and are
                  NOT eligible: Any interface between the tumor and the aorta.

               -  See the protocol for additional clarification and definitions of less and more
                  extensive disease.

        Registration Eligibility Criteria:

          1. Disease Status - Confirmation of radiographic stage as borderline resectable disease
             by real-time Alliance central radiographic review

          2. Prior Treatment

               -  No prior chemotherapy or radiation for pancreatic cancer

               -  No definitive resection of pancreatic cancer

          3. Concomitant Medications

               -  Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on
                  this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for
                  14 days prior to registration on the study. See the protocol for more
                  information.

               -  Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
                  Patients must discontinue the drug 14 days prior to the start of study
                  treatment. See the protocol for more information.

          4. Medical History

               -  No grade ≥ 2 neuropathy

               -  No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism

               -  No uncontrolled gastric ulcer disease (Grade 3 gastric ulcer disease) within 28
                  days of registration

          5. Pregnancy and Nursing Status - Not pregnant and not nursing, because this study
             involves an agent that has known genotoxic, mutagenic and teratogenic effects.
             Therefore, for women of childbearing potential only, a negative pregnancy test done ≤
             7 days prior to registration is required.

          6. Age ≥ 18 years

          7. ECOG Performance Status 0 or 1

          8. Required Initial Laboratory Values:

               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

               -  Platelet Count ≥ 100,000/mm3

               -  Creatinine ≤ 1.5 x upper limit of normal (ULN) or

               -  Calc. Creatinine Clearance > 45 mL/min

               -  Total Bilirubin ≤ 2.0 mg/dL

               -  AST / ALT ≤ 2.5 x ULN
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:overall survival rate at 18 month
Time Frame:at 18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:event-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:R0 resection rate
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:pathologic complete response rate
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:incidence of adverse events per Common Terminology Criteria for Adverse Events version 4
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

Last Updated

April 19, 2017