Know Cancer

forgot password

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

Phase 1
21 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

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


- Determine the safety and tolerability of GW786034 in patients with advanced solid

- 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

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.

Inclusion Criteria


- 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



- 21 and over

Performance status

- Karnofsky 70-100%

Life expectancy

- At least 12 weeks


- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9 g/dL


- 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


- Creatinine clearance at least 60 mL/min


- 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


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 21 days after study

- 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

- No psychological, familial, sociological, or geographical condition that would
preclude study compliance


Biologic therapy

- More than 4 weeks since prior immunotherapy

- Concurrent epoetin alfa allowed

- No concurrent anticancer biologic therapy


- 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


- More than 4 weeks since prior radiotherapy

- No concurrent anticancer radiotherapy


- More than 4 weeks since prior major surgery

- No concurrent surgery for cancer


- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and toxicity assessed weekly during treatment

Safety Issue:


Principal Investigator

Afshin Dowlati, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Case Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

December 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



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