Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

GW786034 in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 21 and over NCI, Pharmaceutical / Industry CASE-CWRU-100231 GSK-VEG10003, GSK-RM2002/00345/02, CWRU-GLAX-1Y02, CWRU-1Y02, NCT00060151, CASE-100231

Objectives

1. Determine the safety and tolerability of GW786034 in patients with advanced solid tumors.
2. Determine the maximum tolerated dose of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.
4. Determine the clinical response in patients treated with this drug.
5. 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.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Safety and toxicity assessed weekly during treatment

Disease response every 9 weeks

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.

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Afshin Dowlati, MD, Protocol chair		Ph: 216-844-1228

Registry Information
Official Title		A Phase I, Open Label, Multiple Dose, Dose Escalation Study OF GW786034 In Patients With Solid Tumors
Trial Start Date		2002-12-13
Registered in ClinicalTrials.gov		NCT00060151
Date Submitted to PDQ		2003-03-19
Information Last Verified		2006-04-01
NCI Grant/Contract Number		CA43703

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