Etoposide and Celecoxib in Patients With Advanced Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Etoposide and celecoxib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving more than 1 drug may be an effective treatment for advanced cancer. PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with etoposide in treating patients with advanced cancer.

Detailed Description
-----------------
OBJECTIVES: To describe the toxicities of the combination of oral etoposide at 50 mg daily with escalating doses of celecoxib in patients with advanced malignancies. To evaluate the effects of the combination of etoposide and celecoxib on plasma levels of vascular endothelial growth factor. OUTLINE: This is a dose-escalation study of celecoxib. In course 1, patients receive oral etoposide once daily on days 1-35 and oral celecoxib twice daily on days 8-35. In all subsequent courses, patients receive oral etoposide 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 by enzyme-linked immunosorbent assay and stored for future analysis of circulating DNA of angiogenic biomarkers by polymerase chain reaction assays.

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

Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: celecoxib
* Drug: etoposide
* Other: immunoenzyme technique
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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 which at the time of study enrollment are controlled and do not require treatment with corticosteroids are eligible PATIENT CHARACTERISTICS: Inclusion criteria: 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 and ALT < 2.0 times upper limit of normal (unless clearly due to the presence of tumor) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Patient must be capable of understanding the nature of the trial and must give written informed consent Exclusion criteria: Unstable or severe intercurrent medical conditions or active, uncontrolled infection History of allergic reactions to non-steroidal anti-inflammatory drugs (NSAIDs) History of bleeding peptic ulcer within the past 3 months PRIOR CONCURRENT THERAPY: Inclusion criteria: Recovered from all prior chemotherapy or radiotherapy Concurrent aspirin for cardiovascular indications allowed More than 2 weeks since prior and no other concurrent NSAIDs Exclusion criteria: Had radiotherapy or chemotherapy within 3 weeks (nitrosoureas or mitomycin C within 6 weeks) prior to anticipated first day of dosing Undergoing concurrent therapy with other investigational agents or antineoplastic therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: etoposide|nan|
|Other: immunoenzyme technique|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

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

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