A Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary Cancer Schema
Condition: Metastatic Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: cohort 1; cohort 2; cohort 3; cohort 4
Intervention description: Weekly gem + GW572016, 1000mg/day (combination); Weekly gem + GW572016, 1500 mg/day (combination); GEMOX + GW572016 1000 mg/day (combination); GEMOX + GW572016 1500 mg/day (combination)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer

Summary:

      A Phase I Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary
      Cancer Schema
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients are required to have histologically or pathologically confirmed, metastatic
             or locally advanced adenocarcinoma of the pancreas or biliary tree

          -  No prior systemic chemotherapy for locally advanced or metastatic pancreaticobiliary
             cancer. No prior EGFR inhibitors.

          -  ECOG performance status 0-2 retain ability to swallow oral medications

          -  Age > 18, non pregnant. Because no dosing or adverse event data are currently
             available on the use of GW572016 in patients <18 years of age, children are excluded
             from this study.

          -  The effects of GW572016 on the developing human fetus at the recommended therapeutic
             dose are unknown. For this reason, women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control or
             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.

        A female is eligible to enter and participate in the study if she is of:

          1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
             including any female who:

               -  Has had a hysterectomy,

               -  Has had a bilateral oophorectomy (ovariectomy),

               -  Has had a bilateral tubal ligation, or

               -  Is post-menopausal(a demonstration of total cessation of menses for ³1 year).

          2. Childbearing potential, has a negative serum pregnancy test at screening, and agrees
             to one of the following:

               -  Intrauterine Device (IUD),

               -  Vasectomized partner who is sterile prior to the female subject's entry and is
                  the sole sexual partner for that female.

               -  Complete abstinence from sexual intercourse for two weeks before exposure to
                  investigational products, throughout the clinical trial, and for at least one
                  week after the last dose of investigational product.

               -  Double barrier contraception (condom with spermicidal jelly, foam, suppository,
                  or film; diaphragm with spermicide; or male condom and diaphragm)

                    -  Adequate hematologic function: ANC≥1500/ul,platelets≥100,000/ul,hemoglobin 8

                    -  Adequate hepatic function with total bilirubin ≤ 1.5mg/dL and ALT or AST ≤
                       2x ULN. (Patients with liver metastases may have AST/ALT less than or equal
                       to 5x upper limit of normal). Patients with elevated bilirubin secondary to
                       biliary obstruction that have subsequently been stented may enter the
                       protocol with a bilirubin of < 2.0 as long as the bilirubin is falling.

                    -  Adequate renal function: (creatinine ≤1.5mg/dL or estimated creatinine
                       clearance greater than 60ml/min calculated by the Cockcroft Formula).

                    -  Cardiac ejection fraction within the institutional range of normal as
                       measured by echocardiogram or MUGA scan. Note that baseline and on treatment
                       scans should be performed using the same modality and preferably at the same
                       institution.

                    -  No peripheral neuropathy for patients who receive oxaliplatin.

                    -  Life expectancy of at least 12 weeks

                    -  Signed informed consent

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          -  Prior treatment with GW572016 or any EGFR targeting therapies.

          -  Prior treatment with systemic chemotherapy for metastatic pancreaticobiliary cancer.

          -  Evidence of brain metastases or leptomeningeal disease

          -  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.

          -  Known contraindications to the use of oxaliplatin or gemcitabine.

          -  History of allergy to platinum compounds in patients receiving oxaliplatin. Amendment
             #2 4/28/05

          -  The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy
             to drugs chemically related to the study drug.

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible pharmacokinetic interactions with GW572016

          -  Participation in any investigational study within 28 days prior to study enrolment

          -  Any major surgery (insertion of a vascular access device is not considered a major
             surgery), hormonal therapy (other than replacement), chemotherapy or radiotherapy
             within the last 4 weeks and/or not recovered from prior therapy within the last 4
             weeks and/or not recovered from prior therapy.

          -  Pregnant or lactating females are excluded from this study because GW572016 is member
             of the 4-anilinoquinazoline class of kinase inhibitors 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
             GW572016, breastfeeding should be discontinued if the mother is treated with GW572016.

          -  Malabsorption syndrome disease significantly affecting gastrointestinal function or
             major resection of the stomach or small bowel that could affect absorption of
             GW572016.

          -  Any unresolved bowel obstruction.

          -  The patient has inadequate venous access in the clinical judgment of the investigator
             or designated clinical staff.

          -  The patient is taking any medication on the prohibited medications list in Section
             10.2 Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided
             there is increased vigilance with respect to monitoring INR. If medically appropriate
             and treatment available, the investigator may also consider switching these patients
             to LMW heparin, where an interaction with GW572016 is not expected.

          -  Patients may not be receiving any other investigational agents or receiving concurrent
             anticancer therapy.