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S1505: Combination Chemotherapy or Gemcitabine Hydrochloride and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

NCT02562716

Description:

This randomized phase II trial studies how well fluorouracil, irinotecan hydrochloride, and oxaliplatin (combination chemotherapy) works and compares to gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, oxaliplatin, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation, 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective than gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating pancreatic cancer.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: S1505: Combination Chemotherapy or Gemcitabine Hydrochloride and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
  • Official Title: A Randomized Phase II Study of Perioperative mFOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel as Therapy for Resectable Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: S1505
  • SECONDARY ID: NCI-2015-01236
  • SECONDARY ID: S1505
  • SECONDARY ID: S1505
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT02562716

Conditions

  • Pancreatic Adenocarcinoma
  • Resectable Pancreatic Carcinoma

Interventions

DrugSynonymsArms
Fluorouracil5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757Arm I (mFOLFIRINOX, surgery)
Gemcitabine HydrochloridedFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011Arm II (gemcitabine, nab-paclitaxel, and surgery)
Irinotecan HydrochlorideCampto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440EArm I (mFOLFIRINOX, surgery)
Oxaliplatin1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669Arm I (mFOLFIRINOX, surgery)
Paclitaxel Albumin-Stabilized Nanoparticle FormulationABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, nab-paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, protein-bound paclitaxelArm II (gemcitabine, nab-paclitaxel, and surgery)

Purpose

This randomized phase II trial studies how well fluorouracil, irinotecan hydrochloride, and oxaliplatin (combination chemotherapy) works and compares to gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, oxaliplatin, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation, 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective than gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating pancreatic cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess 2-year overall survival in each treatment arm (fluorouracil, irinotecan
      hydrochloride, and oxaliplatin [modified (m)FOLFIRINOX] and gemcitabine [gemcitabine
      hydrochloride]/nab-paclitaxel [paclitaxel albumin-stabilized nanoparticle formulation]) in
      patients with resectable pancreatic cancer.

      II. If the stated threshold is met in one or both arms: to choose the better regimen with
      respect to 2-year overall survival.

      SECONDARY OBJECTIVES:

      I. To estimate, for all patients and within treatment arms: frequency and severity of adverse
      events associated with chemotherapy in the perioperative setting.

      II. To estimate, for all patients and within treatment arms: proportion of patients going to
      surgery for resection after preoperative chemotherapy.

      III. To estimate, for all patients and within treatment arms: proportion of patients
      achieving macroscopically complete tumor removal with negative microscopic surgical margins
      (R0) resection after preoperative chemotherapy.

      IV. To estimate, for all patients and within treatment arms: overall response rate following
      preoperative chemotherapy, including confirmed and unconfirmed, complete and partial
      response, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

      V. To estimate, for all patients and within treatment arms: pathologic response rates after
      R0 or macroscopically complete tumor removal with any positive microscopic surgical margin
      (R1) resection.

      VI. To estimate, for all patients and within treatment arms: patterns of recurrence
      (loco-regional, distant) after R0 or R1 resection.

      VII. To estimate, for all patients and within treatment arms: disease-free survival from the
      time of R0 or R1 resection.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours and irinotecan
      hydrochloride IV over 90 minutes on days 1 and 15. Patients also receive fluorouracil IV over
      46 hours on days 1-3 and 15-17. Treatment repeats every 28 days for 3 courses in the absence
      of disease progression or unacceptable toxicity. Patients achieving stable disease or better
      undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8
      weeks following pancreatectomy, patients receive an additional 3 courses of oxaliplatin,
      irinotecan hydrochloride, and fluorouracil treatment in the absence of disease progression or
      unacceptable toxicity.

      ARM II: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
      minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment
      repeats every 28 days for 3 courses in the absence of disease progression or unacceptable
      toxicity. Patients achieving stable disease or better undergo pancreatectomy 4-8 weeks after
      completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy,
      patients receive an additional 3 courses of paclitaxel albumin-stabilized nanoparticle
      formulation and gemcitabine hydrochloride treatment in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (mFOLFIRINOX, surgery)ExperimentalPatients receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 90 minutes on days 1 and 15. Patients also receive 5-fluorouracil IV over 46 hours on days 1-3 and 15-17. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or better undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy, patients receive an additional 3 courses of oxaliplatin, irinotecan hydrochloride, and fluorouracil treatment in the absence of disease progression or unacceptable toxicity.
  • Fluorouracil
  • Irinotecan Hydrochloride
  • Oxaliplatin
Arm II (gemcitabine, nab-paclitaxel, and surgery)ExperimentalPatients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or better undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy, patients receive an additional 3 courses of paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride treatment in the absence of disease progression or unacceptable toxicity.
  • Gemcitabine Hydrochloride
  • Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically proven pancreatic adenocarcinoma;
             histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible

          -  Patients must have measurable disease in the pancreas; computed tomography (CT) scans
             or magnetic resonance imaging (MRIs) used to assess measurable disease must have been
             completed within 28 days prior to registration; all disease must be assessed and
             documented on the baseline tumor assessment form

          -  Patients must have resectable primary tumor based on contrast-enhanced CT or MRI (CT
             or MRI without contrast as part of positron emission tomography [PET]/CT or PET/MRI is
             NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of
             the chest, abdomen, and pelvis, where resectable is defined as:

               -  No involvement of the celiac artery, common hepatic artery, and superior
                  mesenteric artery (and, if present, replaced right hepatic artery)

               -  No involvement, or < 180° interface between tumor and vessel wall, of the portal
                  vein and/or superior mesenteric vein; and patent portal vein/splenic vein
                  confluence

               -  No evidence of metastatic disease

               -  Note: for tumors of the body and tail of the pancreas, involvement of the splenic
                  artery and vein of any degree is considered resectable disease

          -  CT scans or MRIs used to assess disease at baseline must be submitted for central
             review

          -  Patients must have surgical consult to verify patient is a surgical candidate within
             21 days prior to registration

          -  Patients must not have received prior surgery, radiation therapy, chemotherapy,
             targeted therapy, or any investigational therapy for pancreatic cancer

          -  Patients must have a Zubrod performance status of 0-1

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN

          -  Serum albumin >= 3 g/dL

          -  Serum creatinine =< IULN within 14 days prior to registration

          -  Patients with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements will NOT be eligible

          -  No prior malignancy is allowed except for adequately treated basal (or squamous cell)
             skin cancer, in situ cervical cancer, in situ breast (ductal or lobular) cancer, or
             other cancer for which the patient has been disease and treatment-free for two years

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method for up to 3 months after the
             final administered dose of chemotherapy; a woman is considered to be of "reproductive
             potential" if she has had menses at any time in the preceding 12 consecutive months;
             in addition to routine contraceptive methods, "effective contraception" also includes
             heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect
             of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or
             bilateral tubal ligation; however, if at any point a previously celibate patient
             chooses to become heterosexually active during the time period for use of
             contraceptive measures, he/she is responsible for beginning contraceptive measures

          -  Sites must seek additional patient consent for the future use of specimens

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the OPEN registration process the treating institution's identity is
             provided in order to ensure that the current (within 365 days) date of institutional
             review board approval for this study has been entered in the system
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease-free survival (DFS)
Time Frame:Date of surgical resection to the date of first documentation or recurrence (loco-regional or distant) or death due to any cause, assessed up to 4 years
Safety Issue:
Description:Distributions of DFS in each arm will be estimated using the method of Kaplan-Meier.
Measure:Incidence of toxicity by National Cancer Institute Common Terminology Criteria for Adverse Events version 4
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Overall resection rate
Time Frame:Up to 4 years
Safety Issue:
Description:Rates of resection and response can be estimated to within 14% (95% confidence interval).
Measure:Overall response rate per RECIST 1.1
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Pathological response rates
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Patterns of recurrence
Time Frame:Up to 4 years
Safety Issue:
Description:Both locoregional (in the pancreatic bed) and distant (liver, lungs, etc.) recurrence rates will be estimated in each arm. Recurrence rates can be estimated to within 15% (95% confidence interval).
Measure:R0 resection rate
Time Frame:Up to 4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

Last Updated

January 2, 2018