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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00055926
First received: March 6, 2003
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: CP-724,714
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety and Pharmacokinetic/Pharmacodynamic Study of CP-724, 714 In Patients With Metastatic HER2-Overexpressing Breast Cancer

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Enrollment: 9
Study Start Date: January 2003
Study Completion Date: May 2005
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00055926

Locations
United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Carolyn Britten, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00055926     History of Changes
Other Study ID Numbers: CDR0000271533, P30CA016042, UCLA-0209105, PFIZER-A4031001
Study First Received: March 6, 2003
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
recurrent breast cancer
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 16, 2014