Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry UCLA-0209105 PFIZER-A4031001, NCT00055926

Objectives

1. Determine the safety and tolerability of CP-724,714 in patients with metastatic HER2-overexpressing breast cancer.
2. Determine the maximum tolerated dose of this drug in these patients.
3. Determine, preliminarily, any antitumor activity of this drug in these patients.
4. Determine the pharmacokinetics of this drug in these patients.
5. Determine the relationship of drug-related adverse events to pharmacokinetic exposure parameters in these patients.
6. 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.

Entry Criteria

Disease Characteristics:

• 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



• No known or clinically suspected brain metastases or leptomeningeal disease



• No symptomatic edema or third-space fluid (e.g., ascites or pleural effusions)



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• See Chemotherapy
• At least 4 weeks since prior trastuzumab (Herceptin)
  • No more than 2 prior trastuzumab-based regimens for advanced disease
• At least 4 weeks since other prior biologic therapy or immunotherapy
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• 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/m²
• No more than 1 prior anthracycline- or anthracenedione-containing regimen (except with approval of the sponsor)
• No prior high-dose chemotherapy with hematopoietic stem cell transplantation
• No concurrent anticancer chemotherapy

Endocrine therapy

• At least 2 weeks since prior hormonal therapy for the primary disease
  • Concurrent hormone replacement therapy or luteinizing hormone-releasing hormone agonists allowed
• No concurrent anticancer hormonal therapy, including tamoxifen

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to the only disease site that would be assessed for response
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior major surgery (2 weeks for minor surgery)
• No prior partial or complete gastrectomy

Other

• Recovered from prior therapy
• At least 4 weeks since prior investigational treatment
• No concurrent antiarrhythmics
• No concurrent antacids
• No concurrent anticoagulant at therapeutic doses
  • Coumarin or heparin derivatives allowed for the prevention of deep vein thrombosis or port patency
• No other concurrent experimental anticancer medications for breast cancer

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³*
• Platelet count at least 100,000/mm³*

 [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)
• No known hepatitis B or C infection

Renal

• Creatinine no greater than 1.5 times ULN

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• 12-lead ECG with normal tracing
  • No 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
• No 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
• No gastrointestinal abnormality that would require medications (including all antacids)
• No persistent symptoms of an esophageal or digestive disorder

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV infection
• No active infection
• No concurrent uncontrolled systemic disorders or laboratory abnormalities that would preclude study drug safety evaluation
• No mental disorder that would preclude study compliance or ability to give informed consent

Expected Enrollment

A total of 3-20 patients will be accrued for this study within 6 months.

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.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Carolyn Britten, MD, Principal investigator		Ph: 310-825-8195; 888-798-0719

Registry Information
Official Title		A Phase I Safety and Pharmacokinetic/Pharmacodynamic Study of CP-724, 714 In Patients With Metastatic HER2-Overexpressing Breast Cancer
Trial Start Date		2003-01-03
Registered in ClinicalTrials.gov		NCT00055926
Date Submitted to PDQ		2003-01-23
Information Last Verified		2004-10-29
NCI Grant/Contract Number		P30-CA16042

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