RATIONALE: GW786034 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and by stopping blood flow to the tumor.

PURPOSE: Phase I trial to study the effectiveness of GW786034 in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: GW786034  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the safety and tolerability of GW786034 in patients with advanced solid tumors.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the clinical response in patients treated with this drug.
• Evaluate the effect of this drug on biomarkers of angiogenesis activity in order to estimate activity and to determine the minimum biologically active dose in these patients.

OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.

Patients receive oral GW786034 twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-6 patients receive escalating doses of GW786034 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 21 days.

PROJECTED ACCRUAL: Approximately 30-50 patients will be accrued for this study.

Ages Eligible for Study:  21 Years and above,  Genders Eligible for Study:  Both

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

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting

Study chairs or principal investigators

Afshin Dowlati, MD,  Study Chair,  Ireland Cancer Center   

Study ID Numbers:  CDR0000299531; CWRU-100231; GSK-VEG10003; GSK-RM2002/00345/02; CWRU-GLAX-1Y02; CWRU-1Y02; NCT00060151
Record last reviewed:  September 2003
Last Updated:  December 6, 2004
Record first received:  May 6, 2003
ClinicalTrials.gov Identifier:  NCT00060151
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08