Pazopanib hydrochloride in Unspecified Adult Solid Tumor, Protocol Specific - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment

Drug: pazopanib hydrochloride

Detailed Description

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.

Study Type

Interventional

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- North Carolina
  - Durham, North Carolina, United States, 27710
    - Duke Comprehensive Cancer Center
- Ohio
  - Cleveland, Ohio, United States, 44106-5065
    - Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and toxicity assessed weekly during treatment

Secondary Outcome Measures

Outcome Measure
Disease response every 9 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Hurwitz HI, Dowlati A, Saini S, Savage S, Suttle AB, Gibson DM, Hodge JP, Merkle EM, Pandite L. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res. 2009 Jun 15;15(12):4220-7. doi: 10.1158/1078-0432.CCR-08-2740. Epub 2009 Jun 9.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

May 6, 2003

First Submitted That Met QC Criteria