PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer
Metastatic Pancreatic Cancer
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring pancreatic ductal carcinoma(PDA), Pancreatic ductal carcinoma, PEGPH20, Gemcitabine, Nab-paclitaxel
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.
Sites / Locations
- Alabama Oncology
- University of South Alabama Mitchell Cancer Institute
- Banner MD Anderson Cancer Center
- Mayo Clinic - Scottsdale
- Arizona Oncology Associates, PC
- Highlands Oncology Group
- Providence St Joseph Medical Center
- Scripps Cancer Center
- UCSD - Moore's Cancer Center
- Cedars-Sinai Medical Center
- University of California Medical Center
- Saint Helena Hospital
- Pacific Hematology Oncology Associates
- The Oncology Institute of Hope and Innovation
- University of Colorado Cancer Center
- Rocky Mountain Cancer Center
- Stamford Hospital
- Georgetown University Medical Center
- University of Miami, Sylvester comprehensive Cancer Center
- H. Lee Moffit Cancer Center
- Piedmont Hospital
- Loyola University Medical Center
- Norton Cancer Institute - Norton HealthCare Pavilion
- Johns Hopkins University Hospital
- Beth Israel Deaconess Medical Center
- Lahey Clinic
- University of Mass Medical School
- University of Michigan
- Virginia Piper Cancer Institute
- Unniversity of Minnesota
- Research Medical Center
- Washington University School of Medicine
- Comprehensive Cancer Centers of Nevada
- St. Joseph's Regional Medical Center
- Roswell Park Cancer Institute
- North Shore Long Island Jewish Health System
- Mount Sinai Medical Center
- Columbia University Medical Center
- University of Rochester
- Gabrail Cancer Center
- University of Oklahoma Health Science Center
- UPMC Cancer Center
- Greenville Health System
- Texas Oncology - Baylor
- Cancer Care Centers of South Texas
- Texas Oncology
- Columbia Basin Hematology and Oncology
- Seattle Cancer Care Alliance
- NorthWest Medical Specialties, PLLC
- University of Wisconsin Hospitals and Clinics
- Froedtert Hospital, Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Run-in Phase - AG: Nab-paclitaxel + Gemcitabine
Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine
Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine
Participants will receive 3.0 micrograms/kilogram (mcg/kg) PEGPH20 with 125 milligrams/square meter (mg/m^2) NAB and 1000 mg/m^2 GEM as intravenous (IV) infusion. In Cycle 1 Week 1, PEGPH20 will be administered alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15 and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1 8 and 15. NAB+GEM will be given 2 to 4 hours after PEGPH20 dose. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior and 8 to 12 hours after completion of each PEGPH20 infusion.
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM, as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and Day 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning and 8 to 12 hours after the completion of each PEGPH20 infusion.
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to beginning and 8 to 12 hours after completion of each PEGPH20 infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given subcutaneously (SC).
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given SC.