Bortezomib and Celecoxib in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Bortezomib and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with celecoxib may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and celecoxib in treating patients with advanced solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose (MTD) of bortezomib and celecoxib in patients with advanced solid tumors. Secondary Determine the overall pattern of toxicities associated with this combination, including the emergence of any cumulative toxicities, during multiple courses of this regimen. Describe the response rate and duration of response or disease stability during therapy in the subset of patients with measurable disease. Assess changes in plasma/serum sphingosine-1-phosphate, ceramide, and other markers of the apoptotic pathway before and during therapy. OUTLINE: This is a dose-escalation study. Patients receive bortezomib IV on days 1, 4, 8, and 11 or days 1, 8, 15, 22, and 29 and oral celecoxib twice daily on days 1-21 or 1-42. Courses repeat every 21 or 42 days in the absence of disease progression or unacceptable toxicity. Patients are evaluated every 2 courses. Patients achieving complete response (CR) receive 2 additional courses of therapy beyond CR. Cohorts of 3-6 patients receive escalating doses of bortezomib and celecoxib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Official Title
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Phase I Trial of Bortezomib (VELCADE™) and Celecoxib in Patients With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: bortezomib
* Drug: celecoxib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologic or cytologic diagnosis of a malignant neoplasm (solid tumor) arising from any primary site with the exception of bone marrow or lymphoid tissue Recurrent or progressive disease after chemotherapy or radiotherapy Chemotherapy or radiotherapy-naive disease allowed if patient is not a candidate for standard treatment either due to comorbidities or lack of willingness to undergo standard treatment Measurable disease PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min Bilirubin ≤ 2 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active concurrent invasive malignancy No peripheral neuropathy ≥ grade 2 within the past 14 days No hypersensitivity to bortezomib, boron, mannitol, any of the cyclooxygenase (COX-2) inhibitors, sulfa drugs, or other nonsteroidal anti-inflammatory drugs (NSAIDs) No active gastrointestinal (GI) ulcers OR history of GI bleeding resulting from prior therapy with NSAIDs PRIOR CONCURRENT THERAPY: At least 2 weeks since completion of prior radiotherapy No prior bortezomib No other concurrent investigational agents No concurrent chemotherapy, radiotherapy, or anticancer surgery No concurrent immune-enhancing therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: bortezomib|nan|
|Drug: celecoxib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response and disease progression by RECIST criteria before each course |  |  | 

 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