Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer
Brief summary
RATIONALE: CP-724,714 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase I trial to study the effectiveness of CP-724,714 in treating patients who have metastatic HER2-overexpressing breast cancer.
Detailed description
OBJECTIVES: * Determine the safety and tolerability of CP-724,714 in patients with metastatic HER2-overexpressing breast cancer. * Determine the maximum tolerated dose of this drug in these patients. * Determine, preliminarily, any antitumor activity of this drug in these patients. * Determine the pharmacokinetics of this drug in these patients. * Determine the relationship of drug-related adverse events to pharmacokinetic exposure parameters in these patients. * Determine the relationship of changes in serum HER2 extracellular domain and HER2 receptor tyrosine kinase phosphorylation to pharmacokinetic exposure parameters and clinical outcome in patients treated with this drug. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive oral CP-724,714 on days 1 and 3-21 during course 1 and then daily during subsequent courses. Courses repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of CP-724,714 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed for at least 30 days. PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 6 months.
Interventions
DRUGCP-724,714
Sponsors
Pfizer
Jonsson Comprehensive Cancer Center
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed HER2-overexpressing breast cancer * Prior or newly documented HER2 amplification by fluorescence in situ hybridization (FISH) * Progressive metastatic disease * Must have received at least one prior chemotherapy regimen for metastatic breast cancer * At least 1 measurable or evaluable lesion * At least 1 lesion accessible for 2 separate core biopsies for pharmacodynamic evaluation * 18 and over * Male or female * ECOG 0-1 * Life expectancy, More than 3 months * Hematopoietic * Absolute neutrophil count at least 1,500/mm\^3\* * Platelet count at least 100,000/mm\^3\* NOTE: \*Without hematopoietic growth factors or transfusions * Hepatic * Bilirubin no greater than 1.5 mg/dL * AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present) * Renal * Creatinine no greater than 1.5 times ULN OR * Creatinine clearance at least 60 mL/min * Cardiovascular * 12-lead ECG with normal tracing * history of cardiovascular disease (i.e., ischemic heart disease, arrhythmia, or congestive heart failure) unless asymptomatic for the past year with no requirement for antiarrhythmics or a clinically significant medical management change * Gastrointestinal * Able to take oral medication\* Negative pregnancy test * Fertile patients must use effective contraception * At least 4 weeks since prior trastuzumab (Herceptin) * At least 4 weeks since other prior biologic therapy or immunotherapy * At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) * At least 6 months since prior doxorubicin or doxorubicin equivalents without any prior or developing signs or symptoms of cardiomyopathy * No cumulative doses of more than 300 mg/m\^2 * At least 2 weeks since prior hormonal therapy for the primary disease * Concurrent hormone replacement therapy or luteinizing hormone-releasing hormone agonists allowed * At least 4 weeks since prior radiotherapy * At least 3 weeks since prior major surgery (2 weeks for minor surgery) * Recovered from prior therapy * At least 4 weeks since prior investigational treatment * Coumarin or heparin derivatives allowed for the prevention of deep vein thrombosis or port patency
Exclusion criteria
* known or clinically suspected brain metastases or leptomeningeal disease * symptomatic edema or third-space fluid (e.g., ascites or pleural effusions) * known hepatitis B or C infection * significant ECG changes that require medical intervention * QTc interval less than 460 msec * No history of torsade or other symptomatic QTc abnormality * LVEF greater than 50% by MUGA * gastrointestinal abnormality that would require medications (including all antacids) * persistent symptoms of an esophageal or digestive disorder * pregnant or nursing * known HIV infection * active infection * concurrent uncontrolled systemic disorders or laboratory abnormalities that would preclude study drug safety evaluation * mental disorder that would preclude study compliance or ability to give informed consent * No more than 2 prior trastuzumab-based regimens for advanced disease * concurrent immunotherapy * more than 1 prior anthracycline- or anthracenedione-containing regimen (except with approval of the sponsor) * prior high-dose chemotherapy with hematopoietic stem cell transplantation * concurrent anticancer chemotherapy * No concurrent anticancer hormonal therapy, including tamoxifen * prior radiotherapy to the only disease site that would be assessed for response * concurrent radiotherapy * prior partial or complete gastrectomy * concurrent antiarrhythmics * concurrent antacids * concurrent anticoagulant at therapeutic doses * other concurrent experimental anticancer medications for breast cancer
Countries
United States
Outcome results
None listed