Cyclophosphamide and Celecoxib in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with celecoxib may help kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with cyclophosphamide in treating patients with advanced cancer.

Detailed Description
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OBJECTIVES: To describe the toxicities of oral cyclophosphamide when administered with escalating doses of celecoxib in patients with advanced malignancies. To evaluate the effects of this regimen on plasma levels of vascular endothelial growth factor. OUTLINE: This is a dose-escalation study of celecoxib. In the first course, patients receive oral cyclophosphamide once daily on days 1-35 and oral celecoxib twice daily on days 8-35. In all subsequent courses, patients receive oral cyclophosphamide once daily and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline, periodically during treatment, and at time of tumor progression. Samples are analyzed for vascular endothelial growth factor levels and stored for future analysis of circulating DNA of angiogenic biomarkers. After completion of study therapy, patients are followed periodically.

Official Title
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Phase I Trial of Oral Cyclophosphamide in Combination With Celecoxib in Patients With Advanced Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: celecoxib
* Drug: cyclophosphamide
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven diagnosis of a malignant disease for which no satisfactory treatment exists at the time of enrollment Patients with brain metastases that, at the time of study enrollment, are controlled and do not require treatment with corticosteroids are eligible PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy ≥ 3 months ANC > 1.5 x 10^9/L Platelet count > 100 x 10^9/L Creatinine clearance > 50 mL/min Serum bilirubin < 1.5 mg/dL AST or ALT < 2.0 times upper limit of normal (unless clearly due to the presence of tumor) Not pregnant or nursing Fertile patients must use effective contraception Patient must be capable of understanding the nature of the trial and must give written informed consent No unstable or severe intercurrent medical conditions or active, uncontrolled infection No history of allergic reactions to nonsteroidal anti-inflammatory drugs No bleeding peptic ulcer within the past 3 months No allergy to sulfa drugs PRIOR CONCURRENT THERAPY: Recovered from all prior therapy No radiotherapy or chemotherapy within the 3 weeks (nitrosoureas or mitomycin C within 6 weeks) prior to anticipated first day of dosing No concurrent therapy with other investigational agents or antineoplastic therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: cyclophosphamide|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  |  | 
| Maximum tolerated dose |  |  | 
| Survival |  |  | 
| Time to failure |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific