Skip to main content
Eligibility
for people ages 18 years to 120 years
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:

Description

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.

Official Title

EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study

Details

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.

Keywords

Kidney Cancer stage I renal cell cancer stage II renal cell cancer stage III renal cell cancer clear cell renal cell carcinoma papillary renal cell carcinoma Everolimus Sirolimus

Eligibility

For people ages 18 years to 120 years

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

Locations

  • Sutter Auburn Faith Hospital
    Auburn, California, 95602, USA
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, USA
  • Mills - Peninsula Hospitals
    Burlingame, California, 94010, USA
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, USA
  • Valley Medical Oncology Consultants-Castro Valley
    Castro Valley, California, 94546, USA
  • Epic Care-Dublin
    Dublin, California, 94568, USA
  • Northbay Cancer Center
    Fairfield, California, 94533, USA
  • Valley Medical Oncology Consultants-Fremont
    Fremont, California, 94538, USA
  • Washington Hospital
    Fremont, California, 94538, USA
  • Marin Cancer Care Inc
    Greenbrae, California, 94904, USA
  • Marin General Hospital
    Greenbrae, California, 94904, USA
  • Contra Costa Regional Medical Center
    Martinez, California, 94553, USA
  • Fremont - Rideout Cancer Center
    Marysville, California, 95901, USA
  • Mercy UC Davis Cancer Center
    Merced, California, 95340, USA
  • Memorial Medical Center
    Modesto, California, 95355, USA
  • El Camino Hospital
    Mountain View, California, 94040, USA
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, 94040, USA
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, USA
  • Sutter Cancer Research Consortium
    Novato, California, 94945, USA
  • Highland General Hospital
    Oakland, California, 94602, USA
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, USA
  • Bay Area Breast Surgeons Inc
    Oakland, California, 94609, USA
  • Bay Area Tumor Institute
    Oakland, California, 94609, USA
  • Larry G Strieff MD Medical Corporation
    Oakland, California, 94609, USA
  • Tom K Lee Inc
    Oakland, California, 94609, USA
  • Epic Care-Oakland
    Oakland, California, 94612, USA
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, USA
  • Valley Medical Oncology Consultants
    Pleasanton, California, 94588, USA
  • Sutter Roseville Medical Center
    Roseville, California, 95661, USA
  • Sutter General Hospital
    Sacramento, California, 95816, USA
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, USA
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94118, USA
  • Doctors Medical Center- JC Robinson Regional Cancer Center
    San Pablo, California, 94806, USA
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, USA
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, 95403, USA
  • Palo Atlo Medical Foundation-Sunnyvale
    Sunnyvale, California, 94806, USA
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, USA
  • Kaiser Anaheim Medical Center
    Anaheim, California, 92807, USA
  • Kaiser Permanente Medical Group - Baldwin Park
    Baldwin Park, California, 91706, USA
  • Kaiser Foundation Hospital
    Bellflower, California, 90706, USA
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, USA
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, USA
  • Kaiser Permanente Hospital
    Fontana, California, 92335, USA
  • Saint Jude Medical Center
    Fullerton, California, 92835, USA
  • Glendale Memorial Hospital and Health Center
    Glendale, California, 91204, USA
  • Kaiser Permanente - Harbor City
    Harbor City, California, 90710, USA
  • Southern California Permanente Medical Group
    Irvine, California, 92618, USA
  • UC San Diego Moores Cancer Center
    La Jolla, California, 92093, USA
  • Long Beach Memorial Medical Center-Todd Cancer Institute
    Long Beach, California, 90806, USA
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, USA
  • Kaiser Permanente
    Los Angeles, California, 90027, USA
  • Los Angeles County-USC Medical Center
    Los Angeles, California, 90033, USA
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, USA
  • Kaiser Permanente-West Los Angeles
    Los Angeles, California, 90034, USA
  • Cedars-Sinai Medical Center
    Los Angeles, California, 90048, USA
  • Kaiser Permanente - Panorama City
    Panorama City, California, 91402, USA
  • Eisenhower Medical Center
    Rancho Mirage, California, 92270, USA
  • Kaiser Permanente Medical Center
    Riverside, California, 92505, USA
  • Kaiser Permanente-Mission
    San Diego, California, 92108, USA
  • Kaiser Permanente at San Diego
    San Diego, California, 92120, USA
  • Kaiser Permanente
    San Diego, California, 92120, USA
  • Kaiser Permanente Health Care
    San Marcos, California, 92069, USA
  • Tahoe Forest Cancer Center
    Truckee, California, 96161, USA
  • Presbyterian Intercommunity Hospital
    Whittier, California, 90602, USA
  • Kaiser Permanente
    Woodland Hills, California, 91367, USA

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Southwest Oncology Group
ID
NCT01120249
Phase
Phase 3
Study Type
Interventional
Last Updated
October 2016