GW786034 in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00060151
First received: May 6, 2003
Last updated: September 19, 2013
Last verified: April 2006
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: pazopanib hydrochloride
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Multiple Dose, Dose Escalation Study OF GW786034 In Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety and toxicity assessed weekly during treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease response every 9 weeks [ Designated as safety issue: No ]

Study Start Date: December 2002
Study Completion Date: June 2009
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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00060151

Locations
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Afshin Dowlati, MD Case Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00060151     History of Changes
Other Study ID Numbers: CDR0000299531, CASE-CWRU-100231, GSK-VEG10003, GSK-RM2002/00345/02, CWRU-GLAX-1Y02, CWRU-1Y02, CASE-100231
Study First Received: May 6, 2003
Last Updated: September 19, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014