Effect of Esomeprazole on the Pharmacokinetics of BMS-275183 in Patients with Advanced Malignancies

1) Signed written informed consent
2) a). Histologically or cytologically confirmed diagnosis of non-hematological malignancy that has progressed on standard therapy or for whom no standard therapy is known.
b) Measurable or non-measurable disease (defined in Section 3.3.3.2).
c) At least 4 weeks must have elapsed from the last dose of chemotherapy, including monoclonal antibodies that have half-lives of around 2 weeks (e.g., Erbitux*, Herceptin*, Avastin*) and taxanes prior to beginning protocol therapy. At least 6 weeks must have elapsed from the last dose of nitrosoureas, mitomycin C, and liposomal doxorubicin prior to beginning protocol therapy. At least 2 weeks must have elapsed from the last dose of oral targeted anti-cancer agents (e.g., Iressa*, Tarceva*, Gleevec*) before study drug administration. Patients must have recovered to baseline or Grade 1 from the toxicities resulting from previous therapies.
d) Adequate recovery from recent surgery and radiation therapy. At least 1 week must have elapsed from the time of a minor surgery, and at least 3 weeks for major surgery or radiation therapy.
e) ECOG performance status 0-1 (Appendix 1).
f) Life expectancy at least 3 months.
g) Patient must be available for follow-up.
h) Patients must have received no more than 3 prior chemotherapy regimens, which are considered myelotoxic, given in the advanced/metastatic setting. Additional prior chemotherapy given in the adjuvant or neo-adjuvant setting is allowed.;3) Physical and Laboratory Findings
a) Adequate hematologic function with absolute neutrophil counts >= 1,500/mm3, and platelets >= 100,000/mm3.
b) Adequate hepatic function with serum total bilirubin <= 1.5 times the upper institutional limits of normal and ALT <= 2.5 times the upper institutional limits of normal.
c) Adequate renal function with serum creatinine <= 1.5 times the upper institutional limits of normal.;Age and Sex
a) Men and women, ages 18 and greater.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception (female condum, cervical cap, spermicidal jelly or IUD) to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. A barrier method of contraception is required for both males and females while participating in this study.
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

1)a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
b) WOCBP using a prohibited contraceptive method.
c) Women who are pregnant or breastfeeding.
d) Women with a positive pregnancy test on enrollment or prior to study drug administration.
e) Sexually active fertile men who are unwilling or unable to use a barrier contraception (e.g., condom) or whose partners are WOCBP not using an adequate method of birth control from the time of enrollment and for 3 months after participation in the study.;2) Medical History and Concurrent Diseases
a) Prior radiotherapy that involved >= 30% of the bone marrow containing skeleton. A recovery period of at least 3 weeks (at least 4 weeks if given to the brain) after completion of radiotherapy is required prior to enrollment (Appendix 2).
b) Uncontrolled or significant pulmonary or cardiovascular disease, including a recent (<= 6 months) myocardial infarction, any significant degree of congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, any history of prolonged QTc interval.
c) CTCAE Grade 2 or greater neuropathy (motor or sensory) currently, or a prior history of Grade 3 neuropathy.
d) A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
e) Known history of HIV.
f) Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirements for steroids or clinical symptoms of/from brain metastases.
g) Superior vena cava syndrome or tumor obstruction (or near obstruction) of a vital structure.
h) QTc interval > 450 msec on ECG.
i) Any psychiatric or other disorders such as dementia that would prohibit the patient from understanding or rendering informed consent or from fully complying with protocol treatment and follow-up.
j) Inability to swallow capsules.
k) Patients with a known history of gastrointestinal disease (such as partial esophageal, gastric, small, or large bowel obstruction), surgery or malabsorption that could potentially impact the absorption of the study drug; patients requiring the use of a feeding tube.
l) Inability to be venipunctured and/or tolerate venous access.
m) Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.;3) Prohibited Therapies and/or Medications
a) Prior exposure to BMS-275183.
b) Other concurrent chemotherapy, hormonal therapy, immunotherapy regimens or radiotherapy, standard or investigational (Patients may continue to receive hormonal replacement therapy. Patients with prostate cancer receiving LHRH agonist treatment will be permitted to continue treatment with LHRH agonists while on therapy).
c) Use of any of the restricted list of products known to inhibit drug metabolism or drug transport within 5 days prior to enrollment (Appendix 3).
d) Use of any of the restricted list of products known to stimulate drug metabolism or drug transport within 2 weeks prior to enrollment (Appendix 3).
e) Use of any of the restricted list of products to have a risk of Torsades de Pointes within 5 days prior to enrollment (Appendix 4).
f) Use of benzimidazoles (i.e., omeprazole, esomeprazole, lansoprazole, pantoprazole) or metoclopramide within 5 days prior to enrollment and after Cycle 1, Day 15 (Appendix 3).
g) Use of metoclopramide within 5 days prior to enrollment.
h) Use of an oral, injectable, or implantable hormonal contraceptive agent within 3 months of enrollment.;4) Other Exclusion Criteria
a) Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.