Gemcitabine/Taxotere/Xeloda (GTX) With Cisplatin in Subjects With Metastatic Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Gemcitabine; Taxotere; Xeloda; Cisplatin
Intervention description: IV on Days 4 and 11; IV on Days 4 and 11; orally, twice a day Days 1-14; IV Days 4 and 11
Intervention MeSH terms: Gemcitabine; Docetaxel; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Primary Objectives

      To assess the efficacy of the combination of gemcitabine, taxotere, and xeloda (GTX) with
      cisplatin in subjects with metastatic pancreatic cancer based on the progression-free
      survival (PFS) rate at 6 month.

      Secondary Objectives

        -  To assess safety and characterize toxicities of the combination of GTX with cisplatin in
           subjects with metastatic pancreatic cancer.

        -  To estimate disease control rate (DCR), PFS, and overall survival (OS).

        -  To estimate a PFS rate of an expansion cohort testing an alternative schedule.

      Study Design

      This study is a single arm phase II study to assess the efficacy of GTX with cisplatin in
      subjects with metastatic pancreatic cancer. Approximately 38 evaluable subjects will be
      enrolled, 28 in the initial cohort and 10 in the expansion cohort

      The study will have a safety run-in phase consisting of 6 subjects. To ensure that the
      combination is safe, the first six subjects will be treated at DL1 and observed for limiting
      toxicity for the first 2 cycles before continuation with further accrual. After the safety
      run-in, the study will be continuously monitored for adverse events.

      The primary endpoint will be the PFS rate at 6 month, which is defined as the proportion of
      subjects alive, free of disease progression at 6 months. The treatment regimen would be
      considered of insufficient activity for further study in this population if PFS rate at 6
      months is 50% or less, and the minimum required level of efficacy that would warrant further
      study with the proposed regimen is a 75% PFS rate at 6 months. The study design includes
      interim monitoring for futility using a predictive probability approach. We will stop the
      study early if given the information at the interim analysis, it is unlikely that the PFS
      rate at 6 months will be greater than 50% if the study continues to the end.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have histologically or cytologically confirmed metastatic pancreatic
             adenocarcinoma. Subjects with islet cell neoplasms are excluded. Subjects with mixed
             histology will be excluded.

          -  Subject has one or more tumors measurable by CT scan using RECIST 1.1 criteria. MRI is
             acceptable if a CT scan is contraindicated.

          -  Patient must be chemotherapy naïve or must have completed chemotherapy greater than 5
             years prior to enrollment.

          -  Male or non-pregnant and non-lactating female of age >18 years

          -  ECOG performance status <1. ECOG 0 indicates that the patient is fully active and able
             to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that
             the patient is restricted in physically strenuous activity but is ambulatory and able
             to carry out work of a light or sedentary nature

          -  Life expectancy of greater than 12 weeks.

          -  Subjects must have adequate organ and marrow function as defined below:

        WBC ≥ 3,500/mcL Absolute Neutrophil Count ≥1,500/mcL Platelets ≥100 x 10^9/L Hemoglobin ≥ 9
        g/d Total Bilirubin within normal institutional limits Alkaline phosphatase ≤ 2.5 x ULN (≤
        5 X ULN for subjects with documented liver metastases) AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5
        X ULN for subjects with documented liver metastases) Creatinine within normal institutional
        limits OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels
        above institutional normal.

          -  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 she or her partner is participating in this study, she should inform
             her treating physician immediately.

          -  Willingness to undergo a tumor biopsy (implemented after the first 6 patients).

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Subjects who have had any prior chemotherapy within 5 years of enrollment

          -  Subjects who have had radiotherapy for pancreatic cancer.

          -  Age ≥ 76 years

          -  Subjects who are receiving or have received any other investigational agents within 28
             days prior to Day 1 of treatment in this study.

          -  Subject has undergone major surgery, other than diagnostic surgery (i.e.--surgery done
             to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to Day 1
             of treatment in this study.

          -  Subject has known brain metastases unless previously treated and well controlled for
             at least 3 months (defined as stable clinically, no edema, no steroids).

          -  History of hypersensitivity or allergic reactions attributed to compounds of similar
             chemical or biologic composition to gemcitabine, taxotere, xeloda, or cisplatin.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Subject has serious medical risk factors involving any of the major organ systems such
             that the Investigator considers it unsafe for the subject to receive an experimental
             research drug.

          -  Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
             systemic therapy.

          -  Subject has a known history of infection with HIV, hepatitis B, or hepatitis C.

          -  Subject is pregnant or breast feeding.

          -  Subject is unwilling or unable to comply with study procedures.

          -  Subject with an unhealed surgical wound or other clinically significant wound.