Renal Cell Cancer, Stage IV Renal Cell Cancer
Conditions
Keywords
recurrent renal cell cancer
Brief summary
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
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.
Interventions
DRUGcelecoxib
Given orally
BIOLOGICALrecombinant interferon alfa-2b
Given subcutaneously
OTHERpolymerase chain reaction
Correlative studies
OTHERlaboratory biomarker analysis
Correlative studies
OTHERreverse transcriptase-polymerase chain reaction
Correlative studies
OTHERimmunologic technique
Correlative studies
OTHERimmunohistochemistry staining method
Correlative studies
OTHERflow cytometry
Correlative studies
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate Assessed by RECIST Criteria. | at week 4 of cycle 2 and every other cycle thereafter | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | death | Overall survival measured in months and summarized using the Kaplan-Meier method. |
| Duration of Response | end of study | 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. |
| Progression-free Survival | to progression | 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. |
| Number of Patients With Statistically Significant Change in Cellular Immune Parameters From Baseline to 2 Months | at two months from start of treatment | To evaluate the effect of celecoxib and interferon alpha therapy on cellular immune parameters. Absolute change following two cycles of therapy. |
Countries
United States
Participant flow
Recruitment details
Patients accrued from medical clinic from June 2006 through July 2009
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b 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. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Celecoxib and Recombinant Interferon Alpha-2b |
|---|---|
| Age Continuous | 62.9 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 2 / 17 |
Outcome results
Primary
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.
Time frame: at week 4 of cycle 2 and every other cycle thereafter
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b | Objective Response Rate Assessed by RECIST Criteria. | Complete Response | 0 participants |
| Celecoxib and Recombinant Interferon Alpha-2b | Objective Response Rate Assessed by RECIST Criteria. | Partial Response | 3 participants |
| Celecoxib and Recombinant Interferon Alpha-2b | Objective Response Rate Assessed by RECIST Criteria. | Stable Disease | 5 participants |
| Celecoxib and Recombinant Interferon Alpha-2b | Objective Response Rate Assessed by RECIST Criteria. | No Response | 9 participants |
Secondary
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.
Time frame: end of study
Population: Patients who achieved at least a partial response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b | Duration of Response | 8.7 months |
Secondary
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.
Time frame: at two months from start of treatment
Population: Patients that received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b | Number of Patients With Statistically Significant Change in Cellular Immune Parameters From Baseline to 2 Months | 0 participants |
Secondary
Overall Survival
Overall survival measured in months and summarized using the Kaplan-Meier method.
Time frame: death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b | Overall Survival | 14.4 months |
Secondary
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.
Time frame: to progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Celecoxib and Recombinant Interferon Alpha-2b | Progression-free Survival | 5.6 months |