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.

Alabama
Mobile

Gulf Coast MBCCOP

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Colorado
Denver

Colorado Cancer Research Program CCOP

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator

Florida
Pensacola

Sacred Heart Medical Oncology Group - Davis Highway

Tarek Eldawy (Mohamed)
Ph: 850-416-4611

Tarek Eldawy (Mohamed)
Principal Investigator

Illinois
Decatur

Central Illinois CCOP

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Galesburg

Illinois CancerCare-Galesburg Cottage Plaza Office

Nguyet Anh Le-Lindqwister
Ph: 800-793-2262

Nguyet Anh Le-Lindqwister
Principal Investigator

La Grange

Adventist La Grange Memorial Hospital

Renee Helene Jacobs
Ph: 630-856-7526

Renee Helene Jacobs
Principal Investigator

Indiana
South Bend

Northern Indiana Cancer Research Consortium CCOP

Robin T. Zon
Ph: 574-234-5123

Robin T. Zon
Principal Investigator

Massachusetts
Brighton

Steward Saint Elizabeth's Medical Center

Christopher W. Ryan
Ph: 503-494-8487
Email: ryanc@ohsu.edu

Christopher W. Ryan
Principal Investigator

Michigan
Ann Arbor

University of Michigan Comprehensive Cancer Center

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Montana
Billings

Montana Cancer Consortium CCOP

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Nevada
Las Vegas

Nevada Cancer Research Foundation CCOP

John Allan Ellerton
Ph: 702-384-0013

John Allan Ellerton
Principal Investigator

North Carolina
Winston-Salem

Southeast Cancer Control Consortium CCOP

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Ohio
Akron

Akron General Medical Center

Esther Hoogland Rehmus
Ph: 330-344-6348

Esther Hoogland Rehmus
Principal Investigator

Tennessee
Memphis

University of Tennessee Health Science Center

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Washington
Seattle

Group Health Cooperative of Puget Sound Oncology Consortium

Christopher W. Ryan

Christopher W. Ryan
Principal Investigator

Virginia Mason CCOP

Craig R. Nichols
Ph: 503-215-6412
Email: vmmc.cancer_clinical_research@VirginiaMason.org

Craig R. Nichols
Principal Investigator

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.