Patient case: 70-year-old male with Lung cancer. Genetic variant: ERBB2 Amplification. Other conditions: Arthritis.

Clinical trial: CP-724,714 in Treating Patients With Metastatic Breast Cancer

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.

Eligibility: 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

Relevance to patient case: not relevant