GW786034 in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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: This phase I trial is studying the side effects and best dose of GW786034 in treating patients with advanced solid tumors.

Detailed Description
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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.

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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: pazopanib hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pazopanib hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity assessed weekly during treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease response every 9 weeks |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific