Vinorelbine and Celecoxib in Treating Women With Relapsed or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vinorelbine with celecoxib may kill more tumor cells. PURPOSE: Phase I trial to determine the effectiveness of combining vinorelbine with celecoxib in treating women who have relapsed or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of vinorelbine and celecoxib in women with relapsed or metastatic breast cancer. Determine the safety profile of this regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive oral celecoxib twice daily on days 1-21 and oral vinorelbine on days 7, 14, and 21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of celecoxib and vinorelbine 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. PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Official Title
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A Phase I Study of Weekly Administration of Oral Navelbine in Combination With the COX-2 Inhibitor Celebrex in Relapsed and/or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: vinorelbine ditartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast Recurrent or metastatic (stage IV) disease Incurable disease Measurable or evaluable disease Stable brain metastases allowed Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status ECOG 0-1 Life expectancy More than 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL Hepatic Bilirubin normal AST/ALT ≤ 2.5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min No clinically significant proteinuria No impaired renal function Cardiovascular No symptomatic congestive heart failure No unstable angina No cardiac arrhythmia No inadequately controlled hypertension Gastrointestinal No disorder that would alter gastrointestinal motility or absorption No dysphagia Able to swallow tablets or capsules Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No hypersensitivity to celecoxib No prior urticaria, asthma, or other allergic-type reaction after taking aspirin or other nonsteroidal anti-inflammatory drugs No allergy to sulfa No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 weeks since prior trastuzumab (Herceptin®) and recovered No concurrent hematopoietic growth factors Chemotherapy At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior adjuvant or neoadjuvant chemotherapy allowed Prior chemotherapy for recurrent or metastatic disease allowed No prior vinorelbine Endocrine therapy At least 2 weeks since prior hormonal therapy Prior adjuvant or neoadjuvant hormonal therapy allowed Prior hormonal therapy for recurrent or metastatic disease allowed Radiotherapy At least 4 weeks since prior radiotherapy for metastatic disease Prior adjuvant radiotherapy allowed Surgery Not specified Other At least 3 weeks since prior investigational anticancer agents and recovered At least 1 week since prior cyclooxygenase-2 (COX-2) inhibitors, except celecoxib No concurrent administration of any of the following drugs: Lithium Fluconazole Aluminum antacids Magnesium antacids Concurrent H_2 blocking agents or proton pump inhibitors allowed for the treatment of dyspepsia or gastroesophageal reflux disease Concurrent bisphosphonates allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|Patients receive oral celecoxib twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.|
|Drug: vinorelbine ditartrate|Patients receive oral vinorelbine on days 7, 14, and 21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose of vinorelbine and celecoxib in women with relapsed or metastatic breast cancer. |  | Courses (21 days) repeat every 21 days in the absence of disease progression or unacceptable toxicity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer