PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer
Condition: Metastatic Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: PEGPH20; Nab-paclitaxel; Gemcitabine; Dexamethasone; Enoxaparin
Intervention description: PEGPH20 will be administered as per the dose and schedule specified in the respective arms.; Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.; Gemcitabine will be administered as per the dose and schedule specified in the respective arms.; Dexamethasone will be administered as per the dose and schedule specified in the respective arms.; Enoxaparin will be administered as per the dose and schedule specified in the respective arms.
Intervention MeSH terms: Dexamethasone; Paclitaxel; Gemcitabine; Enoxaparin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 279.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pancreatic ductal carcinoma(PDA); Pancreatic ductal carcinoma; PEGPH20; Gemcitabine; Nab-paclitaxel

Summary:

      This study is designed to compare the treatment effect of PEGPH20 combined with
      nab-paclitaxel (NAB) and gemcitabine (GEM) [PAG] to NAB and GEM [AG] in participants with
      Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA).

      The study will have 2 run-in phases, one for each formulation of PEGPH20 (original and new
      formulations), and a Phase 2 portion. The 2 run-in phases will evaluate the safety and
      tolerability of the PAG treatment using the original and new succinic acid PEGPH20
      formulation, respectively, compared with AG treatment. Phase 2 will have 2 stages due to a
      partial clinical hold that occurred from April through July 2014. The participants will be
      randomized in 3:1 for the run-in phases. The first stage will randomize participants in a 1:1
      ratio. The second stage will randomize participants in a 2:1 ratio (PAG:AG).

      This is an open-label study. To minimize bias to the progression-free survival endpoint,
      disease progression will be based on the assessment of the Central Imaging Reader (CIR).
      Determination of clinical progression by the Investigator without corresponding CIR
      confirmation will be documented with the relevant signs and symptoms.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Signed Informed consent.

          -  Histologically confirmed Stage IV PDA with documented disseminated neoplasm to liver
             and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose.

          -  One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST
             v.1.1 , excluding the primary pancreatic lesion.

          -  No previous radiotherapy, surgery, chemotherapy or investigational therapy for the
             treatment of metastatic disease.

          -  Karnofsky Performance Status greater than or equal to (≥) 70%.

          -  Life expectancy ≥3 months.

          -  Age ≥18 years.

          -  Screening laboratory values of hemoglobin, platelets, absolute neutrophil count (ANC),
             bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum
             creatinine, serum albumin, prothrombin time/international normalized ratio (INR), and
             partial thromboplastin time (PTT) within specified values/criteria per protocol prior
             to dosing.

        Key Exclusion Criteria:

          -  Non-metastatic PDA.

          -  Evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or other known
             thromboembolic event present during screening period.

          -  Known central nervous system involvement or brain metastasis.

          -  New York (NY) Heart Association Class III or IV cardiac disease or myocardial
             infarction within the past 12 months.

          -  Prior history of cerebrovascular accident or transient ischemic attack.

          -  Pre-existing carotid artery disease.

          -  Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.

          -  Current use of megestrol acetate (use within 10 days of Day 1).

          -  Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C.

          -  History of another primary cancer within the last 3 years with the exception of
             non-melanoma skin cancer, early state prostate cancer, or curatively-treated cervical
             cancer in-situ.

          -  Contraindication to heparin as per National Comprehensive Cancer Network (NCCN)
             guidelines.

          -  Previous major bleed (bleeding requiring transfusion of red blood cells) on
             low-molecular weight heparin (LMWH).

          -  Any other disease, metabolic dysfunction, physical examination finding or clinical
             laboratory finding that leads to reasonable suspicion of disease or condition that
             contraindicates the use of an investigational drug, that may affect interpretation of
             results, or render the participant at a high risk of treatment complications.