Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Jonsson Comprehensive Cancer Center at UCLA

Carolyn Britten

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00055926
Information obtained from ClinicalTrials.gov on December 14, 2011

Back to Top