Gemcitabine Hydrochloride, Nab-Paclitaxel, PEGPH20, and Rivaroxaban in Treating Patients with Stage III-IV Pancreatic Cancer That Cannot Be Removed by Surgery
- Signed, written Institutional Review Board (IRB)-approved informed consent form (ICF)
- Histologically confirmed locally advanced unresectable (stage III) or stage IV pancreatic ductal adenocarcinoma (PDAC)
- Measurable or evaluable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version (v)1.1
- For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted; for patients with metastatic disease, prior treatment for non-metastatic disease with 5-fluorouracil (5-FU) or gemcitabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no >= grade 2 treatment-related toxicities are present
- Karnofsky performance status >= 70%
- Life expectancy >= 3 months
- A negative serum pregnancy test, if female of reproductive potential
- Total bilirubin =< 1.5 times upper limit of normal (ULN) (performed within 14 days prior to day 1)
- Aspartate aminotransferase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ([ALT]; serum glutamic pyruvate transaminase [SGPT]) =< 2.5 times ULN, (if liver metastases are present, then =< 5 times ULN is allowed) (performed within 14 days prior to day 1)
- Serum creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 60 mL/min (performed within 14 days prior to day 1)
- Serum albumin >= 3.0 g/dL (performed within 14 days prior to day 1)
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (performed within 14 days prior to day 1)
- Platelet count >= 100,000 plt/mm^3 (performed within 14 days prior to day 1)
- Hemoglobin >= 9 g/dL (performed within 14 days prior to day 1)
- Prothrombin time (PT)/international normalized ratio (INR) within normal limits (+/- 15%) or within therapeutic range if on warfarin (performed within 14 days prior to day 1)
- Partial thromboplastin time (PTT) within normal limits (+/- 15%) (performed within 14 days prior to day 1)
- For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study; effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods; abstinence alone is not considered an adequate contraceptive measure for the purposes of this study
- Known central nervous system involvement or brain metastases
- New York Heart Association class III or IV cardiac disease or myocardial infarction within the past 12 months
- Known, clinically significant carotid artery disease
- Known, increased risk of bleeding
- Patients with TE event occurring > 6 months prior to enrollment and receiving active anticoagulation
- Patients with any prior history of arterial thrombosis or symptomatic pulmonary embolism
- Patients with current use of megestrol acetate (use within 10 days of day 1) will be excluded
- Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
- Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C
- Known allergy to hyaluronidase
- Patients with prosthetic heart valves
- Women currently pregnant or breastfeeding
- Intolerance of dexamethasone
- History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ
- History of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
- Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications
- Other unspecified reasons that, in the opinion of the investigator, make the subject unsuitable for the study
- Inability to comply with study and follow-up procedures as judged by the investigator
I. To determine the rate of symptomatic thromboembolic (TE) (venous TE [VTE] and arterial TE [ATE]) events in 2 cohorts of patients treated with gemcitabine hydrochloride (gemcitabine), nab-paclitaxel, PEGPH20 and rivaroxaban.
I. To determine median progression free survival (PFS) in patients treated with gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban.
II. To determine median overall survival (OS) in patients treated with gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban.
III. To determine the response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients treated with gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban.
IV. To determine the cancer antigen (CA) 19-9 response in patients treated with gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban.
V. To determine overall major bleeding rate in each study cohort of patients treated with gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban.
I. To assess treatment effects of gemcitabine, nab-paclitaxel and PEGPH20 based on plasma hyaluronan (HA) levels.
II. To assess relationship between routine and exploratory coagulation studies in patients receiving rivaroxaban, TE events and survival.
Patients receive pegylated recombinant human hyaluronidase PH20 intravenously (IV) over 10-12 minutes on days 1, 4, 8, 11, 15, and 18, nab-paclitaxel IV over 30 minutes on days 2, 8, and 15, and gemcitabine hydrochloride IV over 30 minutes on days 2, 8, and 15 of cycle 1. Patients then receive PEGPH20 IV over 10-12 minutes, nab-paclitaxel IV over 30 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of subsequent cycles. Patients receive rivaroxaban orally (PO) twice daily (BID) on days 1-21 and once daily (QD) on days 22-28 of cycle 1 and QD on days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and every 3 months thereafter.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Kenneth Ho-Ming Yu
- Primary ID 16-1066
- Secondary IDs NCI-2016-01542
- Clinicaltrials.gov ID NCT02921022