Sirolimus in Treating Patients With Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: sirolimus
Intervention description: Treatment with rapamycin will begin on Day 1 at a single flat dose level of 5 mg/day. Rapamycin will be administered continuously without interruption through all cycles in an outpatient setting. Each cycle will last 28 days.
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent pancreatic cancer; stage III pancreatic cancer; stage IV pancreatic cancer; adenocarcinoma of the pancreas

Summary:

      RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth.

      PURPOSE: This phase II trial is studying how well sirolimus works in treating patients with
      advanced pancreatic cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

        Inclusion criteria:

          -  Histologically proven adenocarcinoma of the pancreas

               -  Locally-advanced or advanced disease which has progressed after one prior
                  gemcitabine-containing regimen

          -  Unidimensionally measurable disease (defined as at least one unidimensionally
             measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan) OR
             evaluable disease

          -  Tumor tissue available for IHC assessment OR willingness to undergo a safe biopsy of
             tumor tissue

        Exclusion criteria:

          -  Histologic or cytologic diagnosis that is not consistent with adenocarcinoma,
             including adenosquamous, islet cell, cystadenoma or cystadenocarcinoma, carcinoid, or
             small or large cell carcinoma or lymphoma

          -  Adenocarcinoma arising from a site other than the pancreas (e.g., distal common bile
             duct, ampulla of vater or periampullary duodenum)

          -  Known brain metastases

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  ECOG performance status 0-1

          -  WBC > 3,500 cells/mm³

          -  ANC > 1,500 cells/mm³

          -  Hemoglobin > 9 g/dL

          -  Serum creatinine ≤ 2.0 mg/dL

          -  Bilirubin ≤ 2 mg/dL

          -  ALT, AST, and alkaline phosphatase ≤ 5 times upper limit of normal

          -  Triglycerides and total cholesterol < 2 times upper limit of normal

          -  Not pregnant or nursing

        Exclusion criteria:

          -  Uncontrolled medical conditions that could potentially increase the risk of toxicities
             or complications of this therapy, including immunodeficiency and chronic treatment
             with immunosuppressors

          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, prior surgical procedures affecting absorption, or
             active peptic ulcer disease

          -  Active infections

          -  History of concurrent malignancy or history of a second malignancy within the past 5
             years

          -  Clinically significant cardiovascular disease, including myocardial infarction (within
             12 months prior to randomization), unstable angina, grade II or greater peripheral
             vascular disease, uncontrolled congestive heart failure, or uncontrolled hypertension
             (i.e., systolic blood pressure (BP) > 170 mm Hg, diastolic BP > 95 mm Hg)

        PRIOR CONCURRENT THERAPY:

        Exclusion criteria:

          -  Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer
             therapy

          -  Any previous surgery, excluding minor procedures (e.g., dental work or skin biopsy)
             within 4 weeks of enrollment

          -  Participation in an investigational new drug trial within 1 month of starting trial

          -  Treatment with chemotherapy within 30 days of day 1 treatment

          -  At least 10 days since prior and no concurrent:

               -  Cyclosporine

               -  Diltiazem

               -  Ketoconazole

               -  Rifampin

               -  St. Johns wort

               -  Grapefruit juice

          -  Concurrent phenytoin, carbamazepine, barbiturates, or phenobarbital

          -  No other concurrent investigational or commercial agents