Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with trastuzumab may be a better way to block tumor growth.
PRIMARY OBJECTIVES: I. To determine the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide in patients with stage IV breast cancer. (Phase I) II. To determine the efficacy (overall clinical response rate) of the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide and herceptin (for HER2 neu positive patients) in patients with stage IV breast cancer. (Phase II) SECONDARY OBJECTIVES: I. To assess the treatment related toxicity associated with each dose level of this regimen and assess efficacy (overall clinical response rate). (Phase I) II. To assess the safety (treatment related toxicity) of the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide and herceptin (for HER2 neu positive patients) in patients with stage IV breast cancer. (Phase II) III. To assess time to progression and overall survival following treatment with Doxil and daily oral cyclophosphamide and herceptin (for HER2 neu positive patients). (Phase II) IV. To compare the response rate in patients who are heavily pretreated to the response rate in patients who are less heavily pretreated. OUTLINE: This is a phase I, dose-escalation study of pegylated doxorubicin HCl liposome followed by a phase II feasibility study. Patients receive oral cyclophosphamide once daily on days 1-28 and pegylated doxorubicin HCl liposome IV over 90 minutes on day 1. Treatment repeats every 4-6 weeks in the absence of disease progression or unacceptable toxicity. Some patients with HER2/neu 3+ disease may also receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks at the discretion of the treating physician. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Maximum Tolerated Dose and Optimal Tolerated Dose of Pegylated Liposomal Doxorubicin Hydrochloride (Doxil) When Given in Combination With Cyclophosphamide (Phase I)
The dose level in which 2 or more patients develop treatment-related toxicity of grade 3 or higher OR require a dose adjustment following the first course of treatment
Time frame: Up to 24 weeks
Efficacy as Assessed by the Overall Clinical Benefit Rate
Count of participants with a clinical benefit (i.e., complete response, partial response, and stable disease).
Time frame: 18 months
Safety as Assessed by Grade 1, 2, 3, 4, Fatal Toxicity, Need for Dose Reduction, Treatment Interruption, or Treatment Discontinuation
Count of participants with grade 1, 2, 3, 4, fatal toxicity, need for dose reduction, treatment interruption, or treatment discontinuation
Time frame: Periodically during study treatment, up to 24 weeks
Treatment-related Toxicity (Phase I)
Count of phase I participants with treatment related toxicity.
Time frame: Up to 24 weeks
Time to Progression (Phase II)
Median time to progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or new effusions.
Time frame: Up to 2 years
Progression-free Survival (Phase II)
Kaplan-Meier estimate assessed at 18 months
Time frame: 18 months
Overall Survival (Phase II)
Kaplan-Meier estimate assessed at 18 months
Time frame: 18 months
Comparison of Clinical Benefit Rate in 2 Subgroups--heavily Pre-treated (1 or More Regimens for Advanced Disease) vs Less Heavily Pre-treated (no Regimens for Advanced Disease) (Phase II)
Count of participants with a clinical benefit (i.e., complete response, partial response, and stable disease).
Time frame: Up to 24 weeks
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