A Phase I, Open Label, Multiple Dose, Dose Escalation Study OF GW786034 In Patients With Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced solid tumor

- Refractory to standard therapy or for which no standard therapy exists

- No untreated leptomeningeal or brain metastases

- Previously treated brain metastases are allowed if currently asymptomatic and
patient is off steroids and antiseizure medications for more than 3 months
before study entry

PATIENT CHARACTERISTICS:

Age

- 21 and over

Performance status

- Karnofsky 70-100%

Life expectancy

- At least 12 weeks

Hematopoietic

- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9 g/dL

Hepatic

- Bilirubin no greater than 1.5 mg/dL

- AST and ALT no greater than 2 times upper limit of normal (ULN) (5 times ULN if tumor
involvement)

Renal

- Creatinine clearance at least 60 mL/min

Cardiovascular

- No uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or
diastolic blood pressure greater than 100 mm Hg on 2 consecutive measurements
separated by 1 week)

- No arterial or venous thrombosis (including cerebrovascular accident) within the past
3 months

- No myocardial infarction within the past 3 months

- No unstable angina within the past 3 months

- No cardiac angiopathy or stenting within the past 3 months

- No cardiac pacemaker

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 21 days after study
treatment

- Able to swallow and retain oral medication

- Good venous access

- No prior or concurrent gastrointestinal disease

- No prior or concurrent condition known to interfere with the absorption,
distribution, metabolism, or excretion of drugs

- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to study drug

- No other unstable, pre-existing major medical condition

- No orthopedic pins or rods or other embedded metal that would preclude undergoing an
MRI

- No psychological, familial, sociological, or geographical condition that would
preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior immunotherapy

- Concurrent epoetin alfa allowed

- No concurrent anticancer biologic therapy

Chemotherapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No concurrent anticancer cytotoxic chemotherapy

Endocrine therapy

- See Disease Characteristics

- More than 4 weeks since prior hormonal or steroid therapy (other than replacement)

- No concurrent anticancer hormonal therapy (except for replacement)

- No concurrent dexamethasone or prednisone

Radiotherapy

- More than 4 weeks since prior radiotherapy

- No concurrent anticancer radiotherapy

Surgery

- More than 4 weeks since prior major surgery

- No concurrent surgery for cancer

Other

- Recovered from prior therapy

- More than 4 weeks since prior investigational agents

- More then 28 days since prior alteration of antihypertensive medications

- Concurrent bisphosphonates allowed

- No other concurrent anticancer therapy

- No concurrent antidepressants (e.g., amitriptyline, fluoxetine, or fluvoxamine)

- No concurrent oral hypoglycemics (e.g., glipizide, glyburide, rosiglitazone, or
tolbutamide)

- No concurrent therapeutic anticoagulation (e.g., warfarin at therapeutic doses)

- Low-dose anticoagulation for prophylaxis allowed

- No concurrent cyclosporine

- No concurrent grapefruit juice

- No concurrent amiodarone, mibefradil, phenobarbital, or pioglitazone

- No concurrent Hypericum perforatum (St. John's Wort)

- No concurrent rifabutin or diethyldithiocarbamate

- No concurrent gestodene, mifepristone, or modafinil

- No concurrent herbal supplements, vitamins, or non-traditional compounds