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

• Status: Completed
• Trial end date: 2005-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Pfizer

Criteria

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