Kidney Cancer
Conditions
Keywords
clear cell renal cell carcinoma, stage III renal cell cancer, stage IV renal cell cancer
Brief summary
RATIONALE: PEG-interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving PEG-interferon alfa-2b together with sorafenib may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of PEG-interferon alfa-2b and sorafenib in treating patients with unresectable or metastatic kidney cancer.
Detailed description
OBJECTIVES: Primary * To determine the maximum tolerated dose and toxicity of PEG-interferon alfa-2b and sorafenib tosylate in patients with unresectable or metastatic clear cell renal cell carcinoma. Secondary * To determine the progression-free survival of patients treated with this regimen. * To evaluate, in a preliminary manner, the response rate and overall survival of patients treated with this regimen. * To evaluate the activation of interferon-induced transcription factors in immune cell subsets (including regulatory T cells \[T regs\]) using a novel flow cytometric assay and correlate this information with clinical outcome. * To measure circulating levels of IFN-γ and IL-5 for determination of Th1/Th2 status and CD4+, CD25+, and FoxP3 cell number (T regs) in peripheral blood. OUTLINE: Patients receive PEG-interferon alfa-2b subcutaneously on days 1, 8, 15, 22, 29, 36, 43, and 50. Patients also receive oral sorafenib tosylate 2-3 times daily on days 15-56 of course 1 and on days 1-56 of all subsequent courses. Courses repeat every 56 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and periodically during study for correlative laboratory studies. Peripheral blood mononuclear cells are analyzed for STAT proteins (STAT1, STAT2, STAT3, STAT4, STAT5) and CD4+, CD25+, and FoxP3 regulatory T cells by flow cytometric assays. Samples are also analyzed for the presence of VEGF, VEGFR, IFN-γ, and IL-5 by ELISA assays; baseline expression of Jak-STAT signaling intermediates (Jak1, Tyk2, IFNAR, and IRF9) by immunoblot analysis; and interferon-stimulated gene expression by real time PCR and RT-PCR analysis. After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Interventions
BIOLOGICALPEG-interferon alfa-2b
administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
DRUGSorafenib
GENETICgene expression analysis
GENETICpolymerase chain reaction
GENETICreverse transcriptase-polymerase chain reaction
OTHERflow cytometry
OTHERimmunoenzyme technique
OTHERlaboratory biomarker analysis
Sponsors
Schering-Plough
Thomas Olencki
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
* Must have histologically or cytologically confirmed clear cell renal cell carcinoma (RCC) * Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension and is ≥ 1.0 cm by spiral CT scan * No prior treatment except PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy \> 6 months * Good/intermediate Motzer prognostic status * ANC ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 10.0 g/dL * Total bilirubin ≤ 2.0 mg/dL * AST and ALT \< 2.5 times normal * Creatinine ≤ 1.8 mg/dL OR creatinine clearance \> 50 mL/min * Calcium \< 12 mg/dL (when corrected for serum albumin) * INR \< 1.5 times upper limit of normal * Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% by 2D echo * Pulse oximetry ≥ 90% at rest on room air * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * No evidence of bleeding diathesis * No uncontrolled coagulation disorders * No active infections requiring IV antibiotics * No known HIV, hepatitis C, or hepatitis B * No autoimmune disease requiring ongoing therapy * No requirement for adrenal replacement * No angina (controlled or uncontrolled) * No uncontrolled hypertension * No history of other major medical illnesses including, but not limited to, any of the following: * Cardiac ischemia * Myocardial infarction * Major cardiac arrhythmias * Inflammatory bowel disorders * No other prior malignancy except for previously treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years * No significant psychiatric disease that, in the opinion of the principal investigator, would preclude giving adequate informed consent or render immunotherapy unsafe PRIOR CONCURRENT THERAPY: * No prior treatment for RCC except sunitinib malate * Patients may have progressed or have been intolerant to sunitinib malate * No prior systemic treatment for metastatic disease (other than sunitinib malate) * No prior organ allografts * At least 2 weeks since prior laparoscopic/robotic surgery * At least 4 weeks since prior open nephrectomy * More than 4 weeks since prior and no concurrent radiotherapy or other surgery * More than 4 weeks since prior systemic steroids * More than 2 weeks since prior topical, injected, or inhaled steroids * No concurrent steroid therapy * No concurrent Hypericum perforatum (St. John's wort)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate | up to 2 months |
| Characterize the Toxicity of Peginterferon Alfa-2b and Sorafenib in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma. | up to 2 months |
Secondary
| Measure | Time frame |
|---|---|
| Circulating Levels of IFN-γ and IL-5 for Determination of Th1/Th2 Status and CD4+, CD25+, and FoxP3 Cell Number (T Regs) in Peripheral Blood | Up to 1 year |
| Overall Survival | up to 1 year |
| Response Rate of Patients Receiving Peginterferon Alfa-2b and Sorafenib. | up to 1 year |
| Progression-free Survival of Patients Receiving Peginterferon Alfa-2b and Sorafenib. | up to 1 year |
| Activation of Interferon-induced Transcription Factors in Immune Cell Subsets by Flow Cytometry and Correlation of This Information With Clinical Outcome | up to 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alfa-2b Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
PEG-interferon alfa-2b: administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
Sorafenib
gene expression analysis
polymerase chain reaction
reverse transcriptase-polymerase chain reaction
flow cytometry
immunoenzyme technique
laboratory biomarker analysis | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Peginterferon Alfa-2b |
|---|---|
| Age, Customized Age18-60 | 1 patient |
| Region of Enrollment United States | 1 patients |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Characterize the Toxicity of Peginterferon Alfa-2b and Sorafenib in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma.
Time frame: up to 2 months
Primary
Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate
Time frame: up to 2 months
Secondary
Activation of Interferon-induced Transcription Factors in Immune Cell Subsets by Flow Cytometry and Correlation of This Information With Clinical Outcome
Time frame: up to 1 year
Secondary
Circulating Levels of IFN-γ and IL-5 for Determination of Th1/Th2 Status and CD4+, CD25+, and FoxP3 Cell Number (T Regs) in Peripheral Blood
Time frame: Up to 1 year
Secondary
Overall Survival
Time frame: up to 1 year
Secondary
Progression-free Survival of Patients Receiving Peginterferon Alfa-2b and Sorafenib.
Time frame: up to 1 year
Secondary
Response Rate of Patients Receiving Peginterferon Alfa-2b and Sorafenib.
Time frame: up to 1 year