A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
Condition: Pancreatic Cancer; Biliary Cancer
MeSH terms: Biliary Tract Neoplasms
Intervention: Gemcitabine; 5-FU; Cisplatin
Intervention MeSH terms: Gemcitabine; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gemcitabine, Infusional 5-Fluorouracil,Cisplatin; Advanced Pancreatic and Biliary Cancers; untreated & previously treated pancreatic & biliary cancer.

Summary:

      Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers
      leading to responses in a substantial minority and increasing survival. The use of the
      FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical
      experience within the University of Michigan Pancreatic Program leads to an expectation of
      tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative
      to FOLFIRINOX include:

        1. Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at
           least as good as irinotecan (probably better, especially when delivered by FDR
           [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea,
           nausea/emesis, myelosuppression and alopecia.

        2. Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression,
           mucositis and diarrhea.

        3. Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold
           aggravated dysesthesia.

      Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the
      investigators believe this treatment may be more widely applicable to pancreatic-biliary
      cancer patients, including those with advanced disease as well as being considered for use in
      locally advanced and neo- and adjuvant settings.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma or
             biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder
             carcinoma).

          -  Patients must have clinical/radiologic evidence of metastatic disease.

          -  Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy
             regimen not containing cisplatin. Previous therapy for metastatic disease might have
             included gemcitabine or infusional 5-FU but not both agents.

          -  ECOG (Eastern Cooperative Oncology Group) performance status < 1 (A measure of quality
             of life where 0 represents asymptomatic and 5 represents death).

          -  Patients must have adequate bone marrow (absolute neutrophil count >1,500/mm3,
             platelet count >100,000/mm3) and renal function (serum creatinine < 1.25 x ULN).

          -  Patients must have at least one measurable lesion per RECIST criteria.

          -  Patients must be free of serious concomitant medical disorders incompatible with study
             participation including active infection requiring systemic therapy.

          -  Previous malignancies are permitted provided that they have been treated with curative
             intent and patient is without evidence of active systemic disease.

          -  Patients must be informed of the investigational nature of this study and provide
             written informed consent prior to receiving protocol treatment.

        Exclusion Criteria:

          -  Patients with pre-existing peripheral neuropathy > grade 2 are ineligible.

          -  Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy
             regimen not containing cisplatin.

          -  Previous therapy for metastatic disease might have included gemcitabine or infusional
             5-FU but not both agents.

          -  Serious concomitant medical disorders incompatible with study participation including
             active infection requiring systemic therapy.