S1313, PEGPH20 in Treating Patients With Newly Diagnosed Metastatic Pancreatic Cancer
Condition: Metastatic Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This partially randomized phase I/II trial studies the side effects and best dose of
      pegylated recombinant human hyaluronidase (PEGPH20) when given together with combination
      chemotherapy and to see how well they work compared with combination chemotherapy alone in
      treating patients with newly diagnosed pancreatic cancer that has spread to other places in
      the body. Pegylated recombinant human hyaluronidase may help chemotherapy drugs work better
      by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as
      leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, 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. It is not yet known whether
      combination chemotherapy is more effective with or without pegylated recombinant human
      hyaluronidase in treating pancreatic cancer.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan
      hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the
      optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic
      adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic
      pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with
      mFOLFIRINOX alone. (Phase II)

      SECONDARY OBJECTIVES:

      I. To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20
      and patients receiving mFOLFIRINOX alone in this patient population.

      II. To assess objective tumor response (confirmed and unconfirmed, complete and partial) in
      patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving
      mFOLFIRINOX alone in this patient population.

      III. To determine the frequency, severity, and tolerability of adverse events of mFOLFIRINOX
      with PEGPH20.

      TERTIARY OBJECTIVES:

      I. To explore the correlation of maximum decrease in cancer antigen (CA) 19-9 levels and time
      to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and
      response.

      II. To explore the correlation of plasma hyaluronan (HA) and tumor expression of HA with
      overall survival, progression-free survival and response.

      OUTLINE: This is a phase I, dose de-escalation study of pegylated recombinant human
      hyaluronidase followed by a randomized phase II study.

      PHASE I: Patients receive pegylated recombinant human hyaluronidase intravenously (IV) over
      10 minutes on day 1*; oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and
      irinotecan hydrochloride IV over 1.5 hours on day 2; and fluorouracil IV over 46 hours on
      days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable
      toxicity.

      PHASE II: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and
      irinotecan hydrochloride IV over 1.5 hours on day 2, and fluorouracil IV over 46 hours on
      days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients receive pegylated recombinant human hyaluronidase IV over 10 minutes on day
      1* and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil as in Arm
      I. Courses repeat every 14 days in the absence of disease progression or unacceptable
      toxicity.

      *NOTE: Some patients also receive pegylated recombinant human hyaluronidase on day 3 or 4 of
      courses 1 and 2.

      After completion of study treatment, patients are followed up for 3 years.
    

Intervention name(s): PEGPH20; Oxaliplatin; Leucovorin; Irinotecan; 5-fluorouracil
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 3 ug/kg on Day 1, IV over 15 minutes; 85 mg/m^2, on Day 2, IV over 2 hours; 400 mg/m^2, on Day 2, IV over 2 hours; 180 mg/m^2, on Day 2, IV over 1.5 hours; 2,400 mg/m^2, Days 2-4, IV over 46 hours
Other intervention name(s): Pegylated Recombinant Human Hyaluronidase; Eloxatin; NSC-266046; leucovorin calcium; CPT-11; NSC-616348; 5-FU; Adrucil; NSC-19893
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Irinotecan; Levoleucovorin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment