Study Of Safety And Tolerability Of GW786034 Given With Lapatinib In Cancer Patients

Inclusion criteria:

• Histologically or cytologically confirmed diagnosis of advanced solid tumor refractory to standard therapy or for whom there is no standard therapy.

• Females are eligible if they are of:

  a) Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

• had a hysterectomy.
• had a bilateral oophorectomy (ovariectomy).
• had a bilateral tubal ligation.
• is post-menopausal (a demonstration of total cessation of menses for 1 year).
• childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following:
• an IUD with a documented failure rate of less than 1% per year.
• vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.
• complete abstinence from sexual intercourse for 14 days before exposure to investigational product, throughout the clinical trial, and for at least 14 days 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 with spermicide).
• ECOG (Eastern Cooperative Oncology Group) PS 0 or 1.
• Adequate bone marrow function.
• Platelets greater than or equal to 75,000/mm3.
• ANC greater than or equal to 1,500/mm3 (1.5 x 109/L).
• Hgb greater than or equal to 9 g/dL (5 mmol/L).
• CLcr > 50 mL/min as calculated by the Cockcroft-Gault formula.
• Total bilirubin less than or equal to 1.5 x upper limit of normal.
• PT/INR/PTT less than or equal to 1.2 x upper limit of normal.
• AST/ALT less than or equal to 3 x upper limit of normal.
• Has LVEF within normal range or above 50% based on MUGA/ECHO.
• Urinalysis for protein is < 2 (negative, trace, or 1). NOTE: If urinalysis is 2 or greater then a 24 hour urine for protein must demonstrate less than 1 gram of protein in 24 hours for patient to be eligible for enrollment.
• Able to swallow and retain oral medication.
• Has a life expectancy of at least 12 weeks.

Exclusion criteria:

• Had prior treatment with either study drug.
• Has brain metastases.
• Uncontrolled hypertension (BP higher than 150/90 SBP/DBP).
• Have heart failure.
• Have DVT (deep vein thrombosis) or arterial thrombosis, MI (myocardial infarction), angina, or has had angioplasty and/or stenting within last 3 months.
• Has allergy to drug similar to lapatinib (e.g. allergic to Iressa(gefitinib) or Tarceva(erlotinib).
• Is using therapeutic doses of anti-coagulant.
• Has had major surgery, hormonal therapy, chemotherapy, radiotherapy, or other investigational agent within last 28 days.
• Pregnant or lactating.
• History or current GI (gastrointestinal) condition that alters stomach or gut emptying from normal (e.g. major surgery on the stomach).
• Bowel obstruction or chronic diarrhea.
• Psychological or geographical conditions that would prevent him/her from being a good candidate.
• Do not have accessible veins for venipuncture.
• History of prolonged QTc on ECG.