Everolimus in Treating Patients with Kidney Cancer Who Have Undergone Surgery

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIITissue collection/Repository, Treatment18 and overS0931
NCI-2011-02028, CDR0000668388, SWOG-S0931, NCT01120249

Trial Description

Summary

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.

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

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

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

Absolute neutrophil count (ANC) >= 1,500/mcL

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

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 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 must not be planning to receive other anti-cancer agents including investigational agents 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

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

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 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 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 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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

SWOG

  • National Cancer Institute
Christopher W. Ryan, Principal Investigator

Trial Sites

U.S.A.

Delaware
Lewes

Beebe Medical Center

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Newark

Christiana Care Health System-Christiana Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Christiana Gynecologic Oncology LLC

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Delaware Clinical and Laboratory Physicians PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Helen F Graham Cancer Center

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Medical Oncology Hematology Consultants PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Regional Hematology and Oncology PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Rehoboth Beach

Beebe Health Campus

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Seaford

Nanticoke Memorial Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Wilmington

Christiana Care Health System-Wilmington Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Maryland
Baltimore

Greater Baltimore Medical Center

Gary Irvin Cohen
Ph: 443-849-3706

Gary Irvin Cohen
Principal Investigator

University of Maryland/Greenebaum Cancer Center

Heather D. Mannuel
Ph: 800-888-8823

Heather D. Mannuel
Principal Investigator

Easton

The Memorial Hospital at Easton

John Patrick Foley
Ph: 410-820-6800ext108
Email: srichter@shorehealth.org

John Patrick Foley
Principal Investigator

Silver Spring

Holy Cross Hospital

Kashif Ali
Ph: 310-754-7552

Kashif Ali
Principal Investigator

New Jersey
Camden

Cooper Hospital University Medical Center

Robert A. Somer
Ph: 856-325-6757

Robert A. Somer
Principal Investigator

East Orange

Veterans Adminstration New Jersey Health Care System

Victor Tsu-Shih Chang
Ph: 800-475-2336
Email: patricia.goyer@med.va.gov

Victor Tsu-Shih Chang
Principal Investigator

Morristown

Morristown Medical Center

Bonni Lee Guerin
Ph: 908-522-2043

Bonni Lee Guerin
Principal Investigator

New Brunswick

Rutgers Cancer Institute of New Jersey

Tina Mayer
Ph: 732-235-8675

Tina Mayer
Principal Investigator

UMDNJ - Robert Wood Johnson University Hospital

Tina Mayer
Ph: 732-235-8675

Tina Mayer
Principal Investigator

Sewell

Kennedy Health Systems-Cancer Center

Trina A. Poretta
Ph: 888-847-8823

Trina A. Poretta
Principal Investigator

Summit

Overlook Hospital

Bonni Lee Guerin
Ph: 908-522-2043

Bonni Lee Guerin
Principal Investigator

Vineland

Inspira Medical Center Vineland

Benjamin P. Negin
Ph: 856-641-7933

Benjamin P. Negin
Principal Investigator

Voorhees

MD Anderson Cancer Center at Cooper-Voorhees

Robert A. Somer
Ph: 856-325-6757

Robert A. Somer
Principal Investigator

Woodbury

Inspira Medical Center Woodbury

Benjamin P. Negin
Ph: 856-641-7933

Benjamin P. Negin
Principal Investigator

Pennsylvania
Abington

Abington Memorial Hospital

Willard G. Andrews
Ph: 215-481-2402

Willard G. Andrews
Principal Investigator

Allentown

Lehigh Valley Hospital-Cedar Crest

Eliot L. Friedman
Ph: 610-402-2273

Eliot L. Friedman
Principal Investigator

Bethlehem

Lehigh Valley Hospital - Muhlenberg

Eliot L. Friedman
Ph: 610-402-2273

Eliot L. Friedman
Principal Investigator

Bryn Mawr

Bryn Mawr Hospital

Albert S. DeNittis
Ph: 866-225-5654

Albert S. DeNittis
Principal Investigator

Danville

Geisinger Medical Center

Christian S. Adonizio
Ph: 570-271-5251

Christian S. Adonizio
Principal Investigator

Doylestown

Doylestown Hospital

Mitchell B. Alden
Ph: 215-345-2378
Email: lheacock@dh.org

Mitchell B. Alden
Principal Investigator

Easton

Easton Hospital

Sonyo Shin
Ph: 610-250-4000

Sonyo Shin
Principal Investigator

Hazleton

Geisinger Medical Center-Cancer Center Hazleton

Christian S. Adonizio
Ph: 570-271-5251

Christian S. Adonizio
Principal Investigator

Hershey

Penn State Milton S Hershey Medical Center

Monika Joshi
Ph: 717-531-3779
Email: CTO@hmc.psu.edu

Monika Joshi
Principal Investigator

Lancaster

Lancaster General Hospital

Shanthi Sivendran
Ph: 717-544-5511

Shanthi Sivendran
Principal Investigator

Lewisburg

Geisinger Medical Oncology at Evangelical Community Hospital

Christian S. Adonizio
Ph: 570-271-5251

Christian S. Adonizio
Principal Investigator

Paoli

Paoli Memorial Hospital

Albert S. DeNittis
Ph: 866-225-5654

Albert S. DeNittis
Principal Investigator

Philadelphia

Fox Chase Cancer Center

Yu-Ning Wong
Ph: 215-728-4790

Yu-Ning Wong
Principal Investigator

Temple University Hospital

Alvaro Pereira-Rico
Ph: 215-728-2983

Alvaro Pereira-Rico
Principal Investigator

Thomas Jefferson University Hospital

Jean H. Hoffman-Censits
Ph: 215-955-6084

Jean H. Hoffman-Censits
Principal Investigator

University of Pennsylvania/Abramson Cancer Center

Naomi Susanne Balzer-Haas
Ph: 800-474-9892

Naomi Susanne Balzer-Haas
Principal Investigator

Pottstown

Pottstown Memorial Medical Center

Wei (Frank) Song
Ph: 610-327-7544

Wei (Frank) Song
Principal Investigator

Pottsville

Geisinger Medical Oncology-Pottsville

Christian S. Adonizio
Ph: 570-271-5251

Christian S. Adonizio
Principal Investigator

Sellersville

Grand View Hospital

Anthony J. Magdalinski
Ph: 215-453-4162
Email: PParsons@gvh.org

Anthony J. Magdalinski
Principal Investigator

West Chester

Chester County Hospital

William Emil Luginbuhl
Ph: 610-431-5297

William Emil Luginbuhl
Principal Investigator

West Reading

Reading Hospital

Terrence Paul Cescon
Ph: 610-988-9323

Terrence Paul Cescon
Principal Investigator

Wilkes-Barre

Geisinger Wyoming Valley/Henry Cancer Center

Christian S. Adonizio
Ph: 570-271-5251

Christian S. Adonizio
Principal Investigator

Williamsport

Susquehanna Cancer Center

Warren Lewis Robinson
Ph: 800-598-4282

Warren Lewis Robinson
Principal Investigator

Wynnewood

Lankenau Medical Center

Albert S. DeNittis
Ph: 866-225-5654

Albert S. DeNittis
Principal Investigator

See All Trial Sites

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01120249

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.