Sorafenib With or Without Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer
Condition: Stage IV Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: sorafenib tosylate; gemcitabine hydrochloride; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Correlative studies
Intervention MeSH terms: Gemcitabine; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II is studying how well giving sorafenib with or without gemcitabine
      works in treating patients with metastatic pancreatic cancer. Sorafenib may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood
      flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving sorafenib together with gemcitabine may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic pancreatic
             carcinoma

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral CT scan

          -  No prior chemotherapy for metastatic disease is allowed; prior adjuvant chemotherapy
             is allowed provided that patients did not receive gemcitabine and the chemotherapy
             completed > 6 months prior to initiation of study therapy

          -  Available tumor biopsy specimen (paraffin embedded or fresh frozen) that was obtained
             at the time of diagnosis and/or prior to study entry is required

          -  Life expectancy of greater than 3 months

          -  ECOG performance status =< 1

          -  Leukocytes >= 3,000/μL

          -  Absolute neutrophil count >= 1,500/μL

          -  Platelets >= 100,000/μL

          -  Hemoglobin >= 9 mg/dL

          -  Total bilirubin =< 1.5 X institutional upper limit of normal

          -  AST(SGOT)/ALT(SGPT) =< 3 X institutional upper limit of normal, unless the liver is
             involved with tumor, in which the AST (SGOT)/ALT (SGPT) must be =< 5 X institutional
             upper limit of normal

          -  Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60
             mL/min/1.73 m^2

          -  The effects of BAY 43-9006 on the developing human fetus at the recommended
             therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents
             as well as other therapeutic agents used in this trial are known to be teratogenic,
             women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Because BAY 43-9006 is at least partially metabolized by the CYP 3A enzyme in the
             liver, the possible effect that inhibitors of CYP 3A may have on BAY 43-9006 is
             unknown; therefore, patients taking inhibitors of CYP 3A (such as ketoconazole,
             itraconazole, and ritonavir) may not be enrolled in this study

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to BAY 43-9006 or gemcitabine

          -  Secondary primary malignancy (except in situ carcinoma of the cervix, in situ cancer
             of the prostate, in situ cancer of the breast or adequately treated nonmelanomatous
             carcinoma of the skin or other malignancy treated at least 5 years previously with no
             evidence of recurrence); concurrent or history of another malignancy =< 5 years

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that
             would limit compliance with study requirements

          -  Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor
             agent with the potential for teratogenic or abortifacient effects; because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the
             mother is treated with BAY 43-9006

          -  Patients with immune deficiency are at increased risk of lethal infections when
             treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken
             in patients receiving combination anti-retroviral therapy when indicated

          -  Patients with evidence of bleeding diathesis

          -  Patients receiving therapeutic doses of anticoagulation; prophylactic anticoagulation
             (i.e. low dose warfarin) of venous or arterial access devices is allowed