Skip to main content

Summary

Eligibility
for people ages 18–120
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 18–120

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

  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94118, United States
  • Epic Care-Oakland
    Oakland, California, 94612, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Breast Surgeons Inc
    Oakland, California, 94609, United States
  • Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Larry G Strieff MD Medical Corporation
    Oakland, California, 94609, United States
  • Tom K Lee Inc
    Oakland, California, 94609, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Marin Cancer Care Inc
    Greenbrae, California, 94904, United States
  • Marin General Hospital
    Greenbrae, California, 94904, United States
  • Highland General Hospital
    Oakland, California, 94602, United States
  • Mills - Peninsula Hospitals
    Burlingame, California, 94010, United States
  • Doctors Medical Center- JC Robinson Regional Cancer Center
    San Pablo, California, 94806, United States
  • Palo Atlo Medical Foundation-Sunnyvale
    Sunnyvale, California, 94806, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants-Castro Valley
    Castro Valley, California, 94546, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Sutter Cancer Research Consortium
    Novato, California, 94945, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, United States
  • Epic Care-Dublin
    Dublin, California, 94568, United States
  • Valley Medical Oncology Consultants-Fremont
    Fremont, California, 94538, United States
  • Washington Hospital
    Fremont, California, 94538, United States
  • Valley Medical Oncology Consultants
    Pleasanton, California, 94588, United States
  • El Camino Hospital
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, United States
  • Northbay Cancer Center
    Fairfield, California, 94533, United States
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, 95403, United States
  • Mercy UC Davis Cancer Center
    Merced, California, 95340, United States
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Sutter Roseville Medical Center
    Roseville, California, 95661, United States
  • Fremont - Rideout Cancer Center
    Marysville, California, 95901, United States
  • Sutter Auburn Faith Hospital
    Auburn, California, 95602, United States
  • Tahoe Forest Cancer Center
    Truckee, California, 96161, United States
  • Reno Oncology Consultants
    Reno, Nevada, 89519, United States
  • Radiation Oncology Associates
    Reno, Nevada, 89509, United States
  • Renown Regional Medical Center
    Reno, Nevada, 89502, United States
  • Alpine Hematology-Oncology
    Reno, Nevada, 89503, United States
  • Saint Mary's Regional Medical Center
    Reno, Nevada, 89503, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California, 91402, United States
  • Kaiser Permanente
    Woodland Hills, California, 91367, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Glendale Memorial Hospital and Health Center
    Glendale, California, 91204, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, United States
  • Kaiser Permanente
    Los Angeles, California, 90027, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California, 90048, United States
  • Kaiser Permanente-West Los Angeles
    Los Angeles, California, 90034, United States
  • Los Angeles County-USC Medical Center
    Los Angeles, California, 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, United States
  • Kaiser Permanente Medical Group - Baldwin Park
    Baldwin Park, California, 91706, United States
  • Presbyterian Intercommunity Hospital
    Whittier, California, 90602, United States
  • Kaiser Foundation Hospital
    Bellflower, California, 90706, United States
  • Kaiser Permanente - Harbor City
    Harbor City, California, 90710, United States
  • Long Beach Memorial Medical Center-Todd Cancer Institute
    Long Beach, California, 90806, United States
  • Saint Jude Medical Center
    Fullerton, California, 92835, United States
  • Kaiser Permanente Hospital
    Fontana, California, 92335, United States
  • Kaiser Anaheim Medical Center
    Anaheim, California, 92807, United States
  • Kaiser Permanente Medical Center
    Riverside, California, 92505, United States
  • Southern California Permanente Medical Group
    Irvine, California, 92618, United States
  • Comprehensive Cancer Centers of Nevada-Summerlin
    Las Vegas, Nevada, 89144, United States
  • Summerlin Hospital Medical Center
    Las Vegas, Nevada, 89144, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    Las Vegas, Nevada, 89149, United States
  • Cancer and Blood Specialists-Tenaya
    Las Vegas, Nevada, 89128, United States
  • Comprehensive Cancer Centers of Nevada - Northwest
    Las Vegas, Nevada, 89128, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    Las Vegas, Nevada, 89128, United States
  • Las Vegas Cancer Center-Medical Center
    Las Vegas, Nevada, 89148-2405, United States
  • 21st Century Oncology - Fort Apache
    Las Vegas, Nevada, 89148, United States
  • Cancer and Blood Specialists-Fort Apache
    Las Vegas, Nevada, 89148, United States
  • Comprehensive Cancer Centers of Nevada
    Las Vegas, Nevada, 89148, United States
  • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    Las Vegas, Nevada, 89113, United States
  • University Medical Center of Southern Nevada
    Las Vegas, Nevada, 89102, United States
  • Cancer and Blood Specialists-Shadow
    Las Vegas, Nevada, 89106, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada, 89106, United States
  • Radiation Oncology Centers of Nevada Central
    Las Vegas, Nevada, 89106, United States
  • 21st Century Oncology - Vegas Tenaya
    Las Vegas, Nevada, 89182, United States
  • 21st Century Oncology - Vegas Sunrise
    Las Vegas, Nevada, 89109, United States
  • Children's Specialty Center of Nevada II
    Las Vegas, Nevada, 89109, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    Las Vegas, Nevada, 89109, United States
  • Sunrise Hospital and Medical Center
    Las Vegas, Nevada, 89109, United States
  • Comprehensive Cancer Centers of Nevada - Central Valley
    Las Vegas, Nevada, 89169, United States
  • Radiation Oncology Centers of Nevada Southeast
    Las Vegas, Nevada, 89119, United States
  • Cancer and Blood Specialists-Henderson
    Henderson, Nevada, 89052, United States
  • Comprehensive Cancer Centers of Nevada - Henderson
    Henderson, Nevada, 89052, United States
  • Las Vegas Cancer Center-Henderson
    Henderson, Nevada, 89052, United States
  • Cancer Therapy and Integrative Medicine
    Las Vegas, Nevada, 89121, United States
  • 21st Century Oncology - Henderson
    Henderson, Nevada, 89074, United States
  • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    Henderson, Nevada, 89074, United States
  • Eisenhower Medical Center
    Rancho Mirage, California, 92270, United States
  • Kaiser Permanente Health Care
    San Marcos, California, 92069, United States

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 1, 2016