A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of GW572016 in Combination With Trastuzumab [Herceptin†]
18 Years
N/A
Both
Breast Cancer
Trial Information
A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of GW572016 in Combination With Trastuzumab [Herceptin†]
OBJECTIVES:
Primary
- Determine the optimally tolerated regimen of GW572016 when administered with
trastuzumab (Herceptin^®) in patients with metastatic breast cancer that overexpresses
HER2/neu.
- Determine the safety and tolerability of this regimen in these patients.
Secondary
- Determine the pharmacokinetic parameters of this regimen in these patients.
- Determine the clinical response in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter, dose-escalation study of GW572016.
Patients receive oral GW572016 once daily on days 1-28 and trastuzumab (Herceptin^®) IV over
90 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GW572016 until the optimally tolerated
regimen (OTR) is determined. The OTR is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. Once the OTR is determined, 10-18 additional
patients are entered and treated at the OTR.
Patients are followed at 28 days.
PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.
Inclusion Criteria:
- Histologically or cytologically confirmed breast cancer
- Metastatic disease
- Measurable or evaluable disease
- HER2/neu overexpression (2+ or 3+) confirmed by immunohistochemistry and/or HER2
gene amplification by fluorescence in situ hybridization
- Brain metastases treated by surgery and/or radiotherapy allowed provided the
following criteria are met:
- Neurologic status stable 2 weeks after discontinuing dexamethasone
- No concurrent anticonvulsants that induce metabolism (e.g., phenytoin,
carbamazepine, or phenobarbital)
- 18 and over
- Male or female
- Karnofsky 70-100%
- Life expectancy, At least 12 weeks
- Hematopoietic
- Absolute granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if patient has
liver metastases)
- Bilirubin < 1.5 mg/dL
- Creatinine clearance > 30 mL/min
- Cardiovascular
- LVEF > 50%
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study
participation
- Adequate venous access
- Able to swallow and retain oral medication
- Prior adjuvant/neoadjuvant chemotherapy allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin.
- More than 4 weeks since prior radiotherapy
- More than 4 weeks since prior major surgery
- Recovered from all prior therapy
- More than 28 days since prior participation in another investigational study
- More than 28 days since prior investigational drugs
Exclusion Criteria:
- extensive tumor, pleural effusions, or parenchymal masses) resulting in dyspnea at
rest
- uncontrolled brain metastases or leptomeningeal disease
- prior myocardial infarction
- pre-existing cardiac dysfunction (e.g., congestive heart failure)
- clinically significant cardiac disease
- angina pectoris
- symptomatic intrinsic pulmonary disease (e.g., asthma or chronic obstructive
pulmonary disease) resulting in dyspnea at rest
- pregnant or nursing
- active infection
- known hypersensitivity to Chinese Hamster Ovary cell proteins or any component of
this product
- known immediate or delayed hypersensitivity reaction or idiosyncrasy to products of
similar chemical composition as study drug
- known contraindications to trastuzumab (Herceptin^®)
- malabsorption syndrome
- disease significantly affecting gastrointestinal function
- psychiatric disorder that would preclude study compliance
- other serious illness or condition
- concurrent biologic therapy
- prior cumulative dose of doxorubicin > 400 mg/m^2 (including liposomal doxorubicin)
- concurrent hormonal therapy*
- concurrent glucocorticoids
- concurrent radiotherapy
- prior major resection of the stomach or small bowel that could affect absorption of
GW572016
- concurrent cytotoxic therapy
- other concurrent anticancer therapy
- other concurrent investigational drugs during and for 28 days after study treatment
- concurrent administration of any of the following medications or substances:
- Antibiotics
- Clarithromycin
- Erythromycin
- Troleandomycin
- Ciprofloxacin
- Rifampin
- Norfloxacin
- Rifabutin
- HIV antivirals
- Delaviridine
- Indinavir
- Nelfinavir
- Ritonavir
- Saquinavir
- Efavirenz
- Nevirapine
- Amprenavir
- Lopinavir
- Anticonvulsants
- Phenytoin
- Carbamazepine
- Phenobarbital
- Antidepressants
- Fluoxetine
- Nefazodone
- Fluvoxamine
- Antifungals
- Itraconazole
- Ketoconazole
- Fluconazole
- Voriconazole
- Antacids (within 1 hour before and after study drug administration)
- Cimetidine
- Amiodarone
- Diltiazem
- Pioglitazone
- Hypericum perforatum (St. John's wort)
- Grapefruit or grapefruit juice
- Rifabutin
- Diethyldithiocarbamate
- Gestodene
- Mifepristone
- Modafinil
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Mark D. Pegram, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000367118
NCT ID:
NCT00085020
Start Date:
March 2004
Completion Date:
February 2005
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- male breast cancer
- recurrent breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
