Study of Safety and Tolerability of PCI-27483 in Patients With Pancreatic Cancer Patients Receiving Treatment With Gemcitabine
Condition: Pancreatic Cancer; Ductal Adrenocarcinoma; Exocrine Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: PCI-27483; Gemcitabine
Intervention description: Part A: Closed to enrollment.Part B: Approximately 20 patients will be randomized to the control arm that will receive a standard regimen of gemcitabine and 20 patients will be randomized to the PCI-27483 arm and treated with both gemcitabine and PCI-27483. PCI-27483 will be administered as subcutaneous (SC) injections, nominally at a dosage of 1.2 mg/kg BID. Patients receiving PCI-27483 with a tumor response or stable disease at 12 weeks will have the option to continue PCI-27483 treatment until disease progression or the investigator considers the study treatment no longer tolerable. Treatment with gemcitabine may continue per standard of care.
All evaluable patients will roll over into Part C at week 16 (Day 113±5). If 2 consecutive INRs at 2 hours postdose are >3.50,a reduced dosage will be calculated.
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PCI-27483; Factor VIIa; Gemcitabine; 4 months life expectancy; Pharmacyclics; Locally Advanced; Metastatic disease

Summary:

      The purpose of this study is to evaluate the safety and tolerability of selected dose
      1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or
      locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously
      administered gemcitabine for 12 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men or women at least 18 years old

          2. Body weight ≥ 40 and ≤ 100 kg.

          3. Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed ≤ 4 months prior to
             enrollment. (Locally advanced does not have any criteria)

          4. Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed ≤ 3 months
             prior to enrollment or metastatic ductal adenocarcinoma diagnosed ≤ 2 months.

          5. Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria.

          6. Patients after non-curative surgery are eligible if at least 4 weeks after surgery and
             recovered from significant surgical morbidity.

          7. Estimated life expectancy of at least 4 months.

          8. ECOG performance status 0 to 1.

          9. Normal baseline coagulation function as defined by:

               1. PT 10-16 seconds, and

               2. aPTT 22-38 seconds.

         10. Agree to not participate in contact sports or strenuous activity while taking
             PCI-27483.

         11. Ability to understand the study, willingness to participate in the study for the study
             duration, and ability to provide written informed consent to participate.

        Exclusion Criteria:

          1. History of any clinically significant medical condition that, in the opinion of the
             Principal Investigator, would interfere with the study evaluation or interpretation.

          2. Known history of brain metastases.

          3. Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of
             enrollment.

          4. History of disease progression while being treated with gemcitabine.

          5. Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the
             primary tumor until > 3 months from initiation of treatment.

          6. History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and
             arterial thromboembolism) or other indications for anticoagulant treatment
             (eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local
             thrombus in the mesenteric or portal vein is acceptable.

          7. Uncontrolled hypertension (systolic > 160 or diastolic > 100 mm Hg on medical
             treatment).

          8. Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to
             enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before
             enrollment.

          9. Contraindication to systemic anticoagulation.

         10. Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc.
             within the past 72 hours.

         11. Known history of clinically significant or recurrent bleeding episodes, including
             significant bleeding after surgery, childbirth, or dental extraction.

         12. Patients with documented invasion of adjacent organs by CT scan (e.g. stomach,
             duodenum) are not eligible

         13. Patients known to have esophageal varicose are not eligible

         14. Known history of a congenital coagulation factor deficiency.

         15. Known acquired or hereditary platelet disorder.

         16. Known history of immunodeficiency.

         17. Women of child-bearing potential or sexually active men, unwilling to use adequate
             contraceptive protection during the course of the study.

         18. Pregnant or lactating women (female patients of childbearing potential must have a
             negative serum pregnancy test within 14 days of first day of drug dosing, or if
             positive, pregnancy ruled out by ultrasound).

         19. Laboratory Abnormalities:

               1. Serum creatinine > 2 mg/dL or creatinine clearance < 50 mL/minute (using Cockroft
                  Gault formula)

               2. AST and ALT ≥ 4.0 x upper limit of normal (ULN).

               3. Bilirubin ≥ 3 mg/dL.

               4. Alkaline phosphatase > 5 x ULN.

               5. Albumin < 2.0g/dL.

               6. Hemoglobin < 9.0 g/dL.

               7. Platelet count < 100,000/μL.

         20. Evidence of active gastrointestinal tract bleeding, including guaiac stool
             positivity,excluding hemorrhoidal bleeding

         21. Chronic active hepatitis B or C.

         22. Known HIV infection.

         23. Participation in any study of an investigational device, medication, biologic, or
             other agent within 30 days prior to enrollment, or planned participation within the
             study duration.

         24. Risk factors for, or use of medications known to prolong QTc interval or that may be
             associate with Torsades de Pointes within 7 days of treatment start (see Appendix J.
             Risk Factors for Drug-induced Torsades de Pointes).

         25. QTc prolongation (defined as a QTc ≥ 450 msec) or other significant ECG abnormalities
             including 2nd degree AV block type II, 3rd degree AV block, or bradycardia
             (ventricular rate less than 50 beats/min). If 2 screening ECGs have a QTc ≥ 450 msec,
             the ECGs can be submitted for a centralized, cardiologic evaluation and if determined
             to be < 450 msec then the patient is eligible.