Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Metastatic Pancreatic Cancer Histologically confirmed metastatic adenocarcinoma of the pancreas (at enrollment) 2. Actively on (or about to initiate) first line therapy for metastatic pancreatic cancer (at enrollment) Patients may have had neo-adjuvant and/or chemotherapy that must have been completed >3 months prior to starting first line therapy Patients may be actively on "maintenance" therapy, such as maintenance capecitabine up to starting first line therapy for metastatic disease 3. Radiographically measurable disease (prior to initiation of second-line therapy) 4. Tumor deposits that are clearly accessible for serial tumor biopsies A patient's biopsied lesion must be at least 1cm in diameter (in at least one dimension) (prior to initiation of second-line therapy) 5. Age ≥ 18 years (at enrollment) 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Table 6, Appendix D) (at enrollment) 7. Adequate hepatic, bone marrow, and renal function at the time of enrollment AND at initiation of second line therapy Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 75,000/mm3; Hemoglobin ≥ 9.0 g/dL Patients may have a transfusion of red blood cells to meet the hemoglobin requirement Renal function: Serum creatinine ≤ 1.5 X upper normal limit of institution's normal range OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal Hepatic function: Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 X the upper normal limit of institution's normal range; bilirubin ≤ 1.5 X the upper limit of normal. For patients with known hepatic metastases, AST and ALT ≤ 5 X the upper normal limit of institution's normal range Prothrombin Time and Partial Thromboplastin Time (PTT) must be ≤ 2 X the upper limit of the institution's normal range and International Normalized Ratio (INR) < 2. Subjects on anticoagulation (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator 8. Patients must have fully recovered from all effects of surgery (prior to initiation of second-line therapy). Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator. 9. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential (at enrollment). 10. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures (at enrollment)  Known or suspected brain or central nervous system metastases, irrespective of prior treatment 2. The subject has had another active malignancy within the past three years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding the of individual subjects should be directed to the Study Chair. 3. Clinically significant peripheral neuropathy at the time of enrollment (defined in the NCI Common Terminology for Adverse Events Version 4.0 [CTCAE v4.0] as grade 2 or greater neurosensory or neuromotor toxicity) 4. Patients receiving any other investigational agents. 5. Active severe infection, or known chronic infection with HIV or hepatitis B virus -Patients with chronic Hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient's liver function tests fall within the parameters set in Section 3.2.7.3, Hepatic function 6. Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke within the last 3 months, or a diagnosis of congestive heart failure 7. Life-threatening visceral disease or other severe concurrent disease 8. Women who are pregnant or breastfeeding 9. Anticipated patient survival under 2 months