Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: S-1; gemcitabine hydrochloride
Intervention description: S-1 is given as follows: 25 mg/m2 bid on days 1-7 and 15-21 of the cycle (28 days); Patients will receive gemcitabine at a dose of 1,000 mg/m2 i.v. at a fixed-dose rate (FDR) infusion of 10 mg/m2/minute (100 minutes), once a week for 3 consecutive weeks, followed by one week rest. Each 4 week period is referred to as a treatment cycle
Intervention MeSH terms: Gemcitabine; Tegafur
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent pancreatic cancer; stage III pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer

Summary:

      RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the
      laboratory may help doctors learn more about changes that may occur in DNA and identify
      biomarkers related to cancer. It may also help doctors predict a patient's response to
      treatment and help plan the best treatment.

      PURPOSE: This phase II trial is studying gene expression in predicting treatment response in
      patients receiving gemcitabine and S-1 for locally advanced unresectable or metastatic
      pancreatic cancer.
    

Eligibility criteria:

        Inclusion criteria

          -  Adenocarcinoma of the pancreas that is already or will be histologically or
             cytologically proven.

          -  Patients must have either locally advanced (unresectable) or metastatic disease.

          -  Radiographically measurable disease is not required.

          -  No prior therapy for advanced pancreatic cancer. Treatment given in the adjuvant
             setting (radiation and/or chemotherapy, given either concurrently or systemically)
             does not count as prior therapy as long as progressive disease occurs > 6 months
             following completion of treatment.

          -  Greater than or equal to 18 years of age.

          -  ECOG performance status of 0 or 1 (See Appendix D).

          -  Laboratory criteria:

          -  ANC > 1500/µL

          -  Platelet count > 100,000/µL

          -  Hemoglobin > 9 g/dL (may be transfused or receive epoetin alfa to maintain or exceed
             this level)

          -  INR < 1.5 (except those subjects who are receiving full-dose warfarin

          -  Total bilirubin < 2.0 mg/dL

          -  AST or ALT < 5 times upper limit of normal for subjects with documented liver
             metastases; < 2.5 times the upper limit of normal for subjects without evidence of
             liver metastases

          -  Serum creatinine < 2.0 mg/dL

          -  Serum CA19-9 > 2X upper limits of normal.

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines.

          -  Women or men of reproductive potential must agree to use an effective contraceptive
             method during treatment and for 6 months afterwards.

        Exclusion criteria

          -  Inability to comply with study and/or follow-up procedures

          -  Disease determined to be not amenable to biopsy upon review of radiographs by the
             oncologist and/or interventional radiologist.

          -  Clearly resectable disease in a patient who is an appropriate operative candidate.

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that might affect the
             interpretation of the results of the study or render the subject at high risk from
             treatment complications

          -  Prior systemic therapy for advanced pancreatic cancer

          -  Pregnant (positive pregnancy test) or lactating

          -  Use of anti-neoplastic or anti-tumor agents not part of the study therapy, including
             chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is
             not permitted while participating in this study.

          -  Use of concurrent investigational agents is not permitted.

        S-1 Specific Exclusion Criteria

          -  Is receiving a concomitant treatment with drugs interacting with S-1. The following
             drugs are prohibited because there may be an interaction with S-1:

          -  Sorivudine, brivudine, uracil, dipyridamole, cimetidine, and folinic acid (may enhance
             S-1 activity).

          -  Allopurinol (may diminish S-1 activity).

          -  Phenytoin (S-1 may enhance phenytoin activity).

          -  Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and
             flucytosine activity).

          -  Pilocarpine (may inhibit cytochrome P-450 enzyme 2A6 activity).