Celecoxib and Recombinant Interferon Alfa-2b in Metastatic Kidney Cancer Who Have Undergone Surgery

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Recombinant interferon alfa-2b may interfere with the growth of cancer cells and slow the growth of kidney cancer. Giving celecoxib together with recombinant interferon alpha-2b may kill more tumor cells and be an effective treatment for metastatic kidney cancer. PURPOSE: This phase II trial is studying how well giving celecoxib together with recombinant interferon alfa-2b works in treating patients with metastatic kidney cancer who have undergone surgery.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the objective response rate of interferon alpha plus celecoxib in metastatic RCC patients with 3+ COX-2 tumor immunostaining. SECONDARY OBJECTIVES: I. To compare cellular immune parameters in metastatic RCC patients with 3+ COX-2 tumor immunostaining to patients with < 1+ tumor immunostaining. II. To evaluate the effect of celecoxib and interferon alpha therapy on cellular immune parameters in metastatic RCC patients with 3+ COX-2 tumor immunostaining. OUTLINE: Patients receive oral celecoxib twice daily and recombinant interferon alpha-2b subcutaneously, once daily, 5 times a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II Trial of Celecoxib Plus Interferon Alpha in Metastatic Renal Cell Carcinoma Patients With 3+ COX-2 Tumor Immunostaining

Conditions
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Renal Cell Cancer, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: celecoxib
* Biological: recombinant interferon alfa-2b
* Other: polymerase chain reaction
* Other: laboratory biomarker analysis
* Other: reverse transcriptase-polymerase chain reaction
* Other: immunologic technique
* Other: immunohistochemistry staining method
* Other: flow cytometry


Participation Criteria
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Eligibility Criteria
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Criteria Patients must have histologically-confirmed metastatic renal cell carcinoma Patients must have 3+ (on a scale of 0 to 3+) COX-2 staining in >= 10% of the RCC tumor cells from baseline tumor tissue Patients must not have received any prior cytokine therapy for renal cell carcinoma Patients may have received any number of prior non-cytokine systemic therapies for metastatic RCC Patients must have undergone nephrectomy (radical or partial) All patients must be at least 2 weeks from prior systemic therapy, radiation or major surgery Patients must have measurable disease per RECIST criteria ECOG performance status 0 or 1 Leukocytes >= 3,000/mL Absolute neutrophil count >= 1,500/mL Platelets >= 75,000/mL Total bilirubin =< 1.5x institutional upper limit AST(SGOT)/ALT(SGPT) =< 2.5x institutional upper limit Creatinine =< 2.0x institutional upper limit No significant cardiovascular disease including congestive heart failure (New York Heart Association Class III or IV), active angina pectoris requiring nitrate therapy, uncontrolled dysrhythmias or recent cardiovascular event (defined as any of the following within the previous 6 months: TIA/CVA, MI, vascular surgery) Ability to understand and the willingness to sign a written informed consent document Patients with any untreated CNS metastases are excluded from this clinical trial; patients who have undergone surgery and/or radiation for CNS metastases are eligible for enrollment if they do not have CNS metastases that have not been treated, are at least 2 weeks from treatment of CNS metastases without evidence of CNS disease progression (stable CT scan or MRI) and are off steroids; all patients must undergo an MRI or infused CT scan of the brain prior to enrollment Patients may not be concurrently receiving any other investigational agents Pregnant women; women of childbearing potential must have a negative pregnancy test prior to enrollment and use adequate contraception while on study and for one month thereafter Concurrent systemic steroid therapy is prohibited (inhaled or topical steroids as well as physiologic replacement doses of steroids are permitted) Patients with a history of a severe allergic reaction (defined as a grade 4 rash, a reaction requiring steroids or epinephrine or any degree of airway compromise) to sulfonamide or sulfonamide derivatives drugs are excluded; this includes, but is not limited to, sulfonamide antibiotics such as sulfadiazine, sulfamethoxazole, sulfisoxazole and sulfacetamide and sulfonamide derivatives such as celecoxib, valdecoxib, diuretics (HCTZ, furosemide), sulfonylureas, dorzolamide and sumatriptan Karnofsky >= 70%

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral celecoxib twice daily and recombinant interferon alpha-2b subcutaneously, once daily, 5 times a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: celecoxib<br>* Given orally<br>* Other names: YM 177;Biological: recombinant interferon alfa-2b<br>* Given subcutaneously<br>* Other names: Intron A;Other: polymerase chain reaction<br>* Correlative studies<br>* Other names: PCR;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: reverse transcriptase-polymerase chain reaction<br>* Correlative studies<br>* Other names: RT-PCR;Other: immunologic technique<br>* Correlative studies<br>* Other names: laboratory methods, immunological;Other: immunohistochemistry staining method<br>* Correlative studies<br>* Other names: immunohistochemistry;Other: flow cytometry<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate Assessed by RECIST Criteria. | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started, including baseline). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Objective response will be assessed by RECIST criteria. | at week 4 of cycle 2 and every other cycle thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival measured in months and summarized using the Kaplan-Meier method. | death | 
| Duration of Response | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, including baseline). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented. | end of study | 
| Progression-free Survival | Progression-free survival measured in months and summarized using the Kaplan-Meier method. Time to objective progression will be measured from the start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. | to progression | 
| Number of Patients With Statistically Significant Change in Cellular Immune Parameters From Baseline to 2 Months | To evaluate the effect of celecoxib and interferon alpha therapy on cellular immune parameters. Absolute change following two cycles of therapy. | at two months from start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer