Kidney Cancer Clinical Trial

S0931, Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery

Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PURPOSE: This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.

View Full Description

Full Description

OBJECTIVES:

Primary

to compare recurrence-free survival in renal carcinoma patients randomly assigned to 54 weeks of everolimus versus 54 weeks of placebo after nephrectomy or partial nephrectomy.

Secondary

To compare the overall survival of patients treated with everolimus vs placebo.
To compare qualitative and quantitative toxicity between the two study arms.
To bank tissue and biologic specimens for future study of molecular biomarkers relevant to the AKT/mTOR and other pathways implicated in the pathogenesis of renal carcinoma and to investigate their potential predictive and prognostic value.
To bank blood specimens for the future study of the relationship between steady-state trough levels of everolimus and relevant side effects (lymphopenia, infection, hyperglycemia, hypercholesterolemia, hypertriglyceridemia) in patients treated on this study with everolimus.

OUTLINE: This is a multicenter study.

Patients are stratified according to pathologic stage (intermediate high-risk vs very high-risk), histologic subtype (clear cell vs non-clear cell), and performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral everolimus once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

Archived tumor tissue, plasma, and whole blood samples may be collected periodically for biomarker analysis and other translational studies.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 8 years.

View Eligibility Criteria

Eligibility Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed renal cell carcinoma

Clear cell or non-clear cell allowed

No disease of the collecting duct or medullary carcinoma
Considered pathologically either intermediate high-risk or very high-risk disease
No history of distant metastases
Patients with microvascular invasion of the renal vein of any grade or stage (as long as M0) are eligible

Have undergone a full surgical resection (radical nephrectomy or partial nephrectomy) including removal of all clinically positive nodes

Surgical margins must be negative

Patients with positive renal vein margins are eligible unless there is invasion of the renal vein wall at the margin (provided no other margins are positive)
Patients must be registered within 84 days after the date of the first surgical resection of the first tumor

No evidence of residual or metastatic renal cell cancer on CT scan of the chest, abdomen, and pelvis (all with oral and IV contrast) performed after nephrectomy and within 28 days before registration

MRI scans of the abdomen and pelvis with gadolinium and a non-contrast CT scan of the chest may be substituted if the patient is not able to have CT scans with IV contrast

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Serum creatinine ≤ 2.0 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 30 mL/min
Bilirubin ≤ 1.5 times ULN
SGOT and SGPT ≤ 2.5 times ULN
Not pregnant or nursing
Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment
Able to take oral medications

Patients must not have any of the following:

NYHA class III-IV cardiac disease (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort)
Unstable angina pectoris
Myocardial infarction within the past 6 months
Serious uncontrolled cardiac arrhythmia
Patients must NOT have liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh Class C)
HBV and HCV testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection
Must be able to take oral medications
No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
No known history of HIV seropositivity
No known uncontrolled, underlying pulmonary disease (spirometry and DLCO ≤ 50% of predicted OR oxygen saturation ≤ 88% at rest on room air)

No uncontrolled hyperlipidemia (fasting serum cholesterol > 300 mg/dL AND fasting triglycerides > 2.5 times ULN) obtained within 28 days prior to registration

Optimal lipid control must be achieved before registration and monitored during protocol treatment

No uncontrolled diabetes mellitus (defined by fasting serum glucose > 1.5 times ULN) obtained within 28 days prior to registration.

Optimal glucose control must be achieved before registration and monitored during protocol treatment

No prior malignancies except for any of the following:

Adequately treated basal cell or squamous cell skin cancer
In situ cervical cancer
Adequately treated stage I or stage II cancer from which the patient is currently in complete remission
Any other cancer from which the patient has been disease-free for 5 years
No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to their excipients
No contraindications to receiving either IV iodine-based contrast or gadolinium

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Patients must have recovered from any surgery-related complications
No prior anticancer therapy for renal cell carcinoma including systemic therapy in the adjuvant or neoadjuvant setting, immunotherapy, investigational therapy, surgical metastasectomy, or radiotherapy
More than 14 days since prior and no concurrent strong CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, voriconazole, posaconazole, fluvoxamine, nefazodone, nelfinavir, or ritonavir) or strong CYP3A4 inducers (i.e., phenytoin, rifampin, or rifabutin)
More than 7 days since prior and no concurrent live vaccines
No other concurrent anticancer agents including investigational agents

No concurrent chronic treatment with systemic steroids or another immunosuppressive agent

Topical or inhaled corticosteroids are allowed

Study is for people with:

Kidney Cancer

Phase:

Phase 3

Estimated Enrollment:

1545

Study ID:

NCT01120249

Recruitment Status:

Active, not recruiting

Sponsor:

SWOG Cancer Research Network

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 796 Locations for this study

See Locations Near You

How clear is this clinincal trial information?

Study is for people with:

Kidney Cancer

Phase:

Phase 3

Estimated Enrollment:

1545

Study ID:

NCT01120249

Recruitment Status:

Active, not recruiting

Sponsor:


SWOG Cancer Research Network

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.