Everolimus in Treating Patients with Kidney Cancer Who Have Undergone Surgery

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Status: Closed to Accrual

Description

This phase III trial studies everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed renal cell carcinoma (clear cell or non-clear cell allowed, but collecting duct or medullary carcinomas excluded); patients must be considered pathologically either intermediate high risk or very high risk; patients must not have a history of distant metastases; patients with microvascular invasion of the renal vein of any grade or stage (as long as M0) are also eligible
  • Patients must 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 plan to start study drug within 84 days after the date of full surgical resection; patients must have recovered from any surgical related complications
  • Patients with bilateral renal tumors are eligible provided both tumors have undergone full surgical resection and at least one of the tumors meets all eligibility criteria; patients must plan to start study drug within 84 days after the date of the resection of the first tumor
  • Patients must not have any evidence of residual or metastatic renal cell cancer on computed tomography (CT) scan of the chest, abdomen, and pelvis, all with oral and intravenous (IV) contrast after nephrectomy and within a maximum of 28 days prior to registration; a magnetic resonance imaging (MRI) scan of the abdomen/pelvis with gadolinium and a non-contrast CT of the chest is an acceptable imaging alternative; non-contrast CT of the chest/abdomen/pelvis should only be performed if, in the opinion of the investigator, it is in the best medical interest of the patient to not receive IV contrast of any form; NOTE: positron emission tomography (PET)/CT is not an acceptable imaging alternative; patients who display subcentimeter pulmonary nodules (by CT scan) that are non-specific and considered unlikely to represent metastatic disease by the treating investigator will be considered eligible
  • Patients must not have received any prior anti-cancer therapy (except for radical or partial nephrectomy noted above) for renal cell carcinoma, including systemic therapy in the adjuvant or neoadjuvant setting, immunotherapy, investigational therapy, surgical metastasectomy, or radiation therapy
  • Patients must not be planning to receive other anti-cancer agents including investigational agents while on protocol treatment
  • Patients must not be receiving chronic, systemic treatment with corticosteroids or other immunosuppressive agent; topical or inhaled corticosteroids are allowed
  • Patients must not have received immunization with an attenuated live vaccine within seven days prior to registration nor have plans to receive such vaccination while on protocol treatment
  • Patients must not be taking, nor plan to take while on protocol treatment, strong cytochrome P450, subfamily 3A, polypeptide 4 (CYP3A4) inhibitors, (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, fluvoxamine, nefazodone, nelfinavir, ritonavir) and/or strong CYP3A4 inducers (e.g. phenytoin, rifampin, rifabutin) within 14 days prior to randomization (moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution)
  • Patients must have a complete physical examination and medical history within 28 days prior to registration
  • Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association criteria (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 6 months, or serious uncontrolled cardiac arrhythmia
  • Patients must not have any known uncontrolled underlying pulmonary disease (e.g. forced expiratory volume in 1 second [FEV1] or diffusion capacity of the lung for carbon monoxide [DLCO] 50% or less of predicted OR oxygen [O2] saturation 88% or less at rest on room air)
  • Patients must not have any known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dl
  • Serum creatinine =< 2.0 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 30 mL/min obtained within 28 days prior to registration
  • Bilirubin =< 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN
  • Patients must NOT have liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh Class C); NOTE: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) and hepatitis C virus (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
  • Patients must not have a known history of human immunodeficiency virus (HIV) seropositivity
  • Patients must not have uncontrolled hyperlipidemia (fasting serum cholesterol > 300 mg/dL AND fasting triglycerides > 2.5 x ULN) obtained within 28 days prior to registration; optimal lipid control must be achieved before registration and monitored during protocol treatment
  • Patients must not have uncontrolled diabetes mellitus (defined by fasting serum glucose > 1.5 x ULN) obtained within 28 days prior to registration; optimal glucose control must be achieved before registration and monitored during protocol treatment
  • Patients must be able to take oral medications; patient may not have any 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)
  • Patients must have a Zubrod performance status of 0 or 1
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method during protocol treatment and up to 8 weeks after ending protocol treatment; a woman is considered to be of “reproductive potential” if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, “effective contraception” also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

Locations & Contacts

Alabama

Gulf Coast MBCCOP
Status: Active
Mobile, Alabama
Contact: Christopher W. Ryan

Illinois

AMITA Health Adventist Medical Center
Status: Temporarily closed to accrual
La Grange, Illinois
Contact: Renee Helene Jacobs
Phone: 630-286-5500
Heartland Cancer Research NCORP
Status: Active
Decatur, Illinois
Contact: Christopher W. Ryan
Presence Saint Mary's Hospital
Status: Temporarily closed to accrual
Kankakee, Illinois
Contact: Sylvia V. Velinova Falls
Phone: 815-937-8780

Indiana

Michiana Hematology Oncology PC-Elkhart
Status: Temporarily closed to accrual
Elkhart, Indiana
Contact: Robin T. Zon
Phone: 574-237-1328
Michiana Hematology Oncology PC-Mishawaka
Status: Temporarily closed to accrual
Mishawaka, Indiana
Contact: Robin T. Zon
Phone: 574-237-1328
Michiana Hematology Oncology PC-Plymouth
Status: Temporarily closed to accrual
Plymouth, Indiana
Contact: Robin T. Zon
Phone: 574-237-1328
Michiana Hematology Oncology PC-South Bend
Status: Temporarily closed to accrual
South Bend, Indiana
Contact: Robin T. Zon
Phone: 574-237-1328
Michiana Hematology Oncology PC-Westville
Status: Temporarily closed to accrual
Westville, Indiana
Contact: Robin T. Zon
Phone: 574-237-1328
Northern Indiana Cancer Research Consortium
Status: Active
South Bend, Indiana
Contact: Robin T. Zon
Phone: 574-234-5123

Maryland

Peninsula Regional Medical Center
Status: Temporarily closed to accrual
Salisbury, Maryland
Contact: Paul E. Zorsky
Phone: 410-543-7017 Email: sandra.heineken@peninsula.org

Massachusetts

Lowell General Hospital
Status: Temporarily closed to accrual
Lowell, Massachusetts
Contact: Blair Ardman
Phone: 978-788-7084 Email: ghincks@lowellgeneral.org
Steward Saint Elizabeth's Medical Center
Status: Active
Brighton, Massachusetts
Contact: Christopher W. Ryan
Phone: 503-494-8487 Email: ryanc@ohsu.edu

New Hampshire

LRGHealthcare-Lakes Region General Hospital
Status: Temporarily closed to accrual
Laconia, New Hampshire
Contact: Charles H. Catcher
Phone: 800-339-6484

New York

Columbia University / Herbert Irving Cancer Center
Status: Temporarily closed to accrual
New York, New York
Contact: Edward Paul Gelmann
Phone: 212-305-8615
Rochester General Hospital
Status: Temporarily closed to accrual
Rochester, New York
Contact: Peter W. Bushunow
Phone: 585-922-3536 Email: tia.derosa@rochestergeneral.org

Pennsylvania

Grand View Hospital
Status: Temporarily closed to accrual
Sellersville, Pennsylvania
Contact: Anthony J. Magdalinski
Phone: 215-453-4162 Email: PParsons@gvh.org

Tennessee

University of Tennessee Health Science Center
Status: Active
Memphis, Tennessee
Contact: Christopher W. Ryan

Washington

Capital Medical Center
Status: Temporarily closed to accrual
Olympia, Washington
Contact: Yoshio Inoue
Phone: 425-258-7334
Providence - Saint Peter Hospital
Status: Temporarily closed to accrual
Olympia, Washington
Contact: John A. Keech
Phone: 253-403-2394

Wisconsin

Aurora Cancer Care-Waukesha
Status: Temporarily closed to accrual
Waukesha, Wisconsin
Contact: Rubina Qamar
Phone: 888-709-2080

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. To compare overall survival in those patients randomized to everolimus versus those randomized to placebo.

II. To compare qualitative and quantitative toxicity between the two study arms.

TERTIARY OBJECTIVES:

I. To bank tissue and biologic specimens for future study of molecular biomarkers relevant to the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) and other pathways implicated in the pathogenesis of renal carcinoma and to investigate their potential predictive and prognostic value.

II. 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: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive everolimus orally (PO) once daily (QD) 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 placebo PO QD on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

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

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
SWOG

Principal Investigator
Christopher W. Ryan

Trial IDs

Primary ID S0931
Secondary IDs NCI-2011-02028, SWOG-S0931, CDR0000668388
Clinicaltrials.gov ID NCT01120249

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