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Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentClosed18 and overNCINCI-2011-02603
CDR0000684313, CALGB 90802, P30CA014236, U10CA031946, NCT01198158

Trial Description

Summary

This randomized phase III trial is studying giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor.

Further Study Information

PRIMARY OBJECTIVES:

l. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line VEGFR-TKI treatment.

SECONDARY OBJECTIVES:

I. To compare the progression-free survival and proportion who experience an objective response (defined as cCR + PR) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone.

II. To compare grade 3 or higher toxicity in patients receiving each treatment regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to number of risk factors (i.e., Karnofsky performance status < 80%, corrected serum calcium >= 10 mg/dL, and hemoglobin =< 13 g/dL for male patients or =< 11.5 g/dL for female patients) present (0 vs 1 vs 2-3) and total duration of prior VEGFR tyrosine kinase inhibitor therapy (< 12 weeks vs >= 12 weeks). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive everolimus orally (PO) once daily on days 1-28.

ARM II: Patients receive everolimus PO once daily on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood, urine, and tumor tissue samples may be collected periodically for pharmacogenomic and correlative studies.

After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years.

Eligibility Criteria

Inclusion Criteria:

  • Histologically confirmed renal cell carcinoma
  • Some component of clear cell disease
  • Metastatic or unresectable disease
  • Measurable disease by RECIST criteria, defined as lesions that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT scan
  • Treated with ≥ 1 prior VEGFR tyrosine kinase inhibitor treatment and have progressed or have been intolerant to treatment
  • Available archive tissue for submission
  • No active brain metastases
  • Patients with treated, stable (for ≥ 3 months) brain metastases are eligible provided that they meet the following criteria:
  • No ongoing requirement for steroids
  • No evidence of progression or hemorrhage after treatment for ≥ 3 months as ascertained by clinical examination and brain imaging (MRI or CT scan)
  • Stable doses of anticonvulsants are allowed
  • Treatment may include whole-brain radiotherapy, radiosurgery (Gamma Knife, LINAC, or equivalent), or a combination as deemed appropriate by the treating physician
  • Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within the past 3 months are not eligible
  • Baseline brain imaging (MRI or CT scan) is required
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Granulocytes ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Calculated creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 2.5 times ULN
  • Fasting serum triglycerides ≤ 200 mg/dL
  • Serum cholesterol ≤ 300 mg/dL
  • Fasting serum glucose ≤ 1.5 times ULN
  • Urine protein to creatinine ratio < 1.0 OR urine protein ≤ 1+
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
  • No arterial thrombotic events within the past 6 months, including any of the following:
  • Transient ischemic attack
  • Cerebrovascular accident
  • Peripheral arterial thrombus
  • Unstable angina or angina requiring surgical or medical intervention within the past 6 months
  • Myocardial infraction
  • Clinically significant peripheral artery disease (i.e., claudication on < 1 block)
  • Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)
  • Any other arterial thrombotic event
  • Patients who experienced a deep venous thrombosis or pulmonary embolus within the past 6 months are eligible provided that they are on stable therapeutic anticoagulation
  • No inadequately controlled hypertension (defined as a BP of ≥ 160 mm Hg systolic and/or ≥ 90 mm Hg diastolic on medication) or any history of hypertensive crisis or hypertensive encephalopathy
  • No NYHA class II-IV congestive heart failure
  • No known severe impairment of lung function, defined as dyspnea or cough ≥ grade 2 and meeting 1 of the following criteria:
  • Requirement for supplemental oxygen
  • In cases where pulmonary function or pulse oximetry tests have been obtained, FEV1 or forced vital capacity is < 50% of predicted, or single breath DLCO is < 35% of predicted, or resting room oxygen saturation is < 90%
  • No active or severe liver disease (e.g., acute or chronic hepatitis, cirrhosis)
  • No positive serology for anti-hepatitis B core or anti-hepatitis C virus antibodies
  • Hepatitis B virus (HBV) seropositive patients (HB surface antigen positive) are eligible provided that they are closely monitored for evidence of active HBV infection by HBV DNA testing and agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until ≥ 4 weeks after the last dose of everolimus
  • No active bleeding or chronic hemorrhagic diathesis or increased risk for bleeding including, but not limited to, history of major bleeding within the past 6 months (e.g., gastrointestinal [GI], lung, or CNS sites or required transfusion support)
  • No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 6 months
  • No serious non-healing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 4 weeks
  • No concurrent hormones or other chemotherapeutic agents except for steroids given for adrenal failure, suspected drug-induced pneumonitis, or other allergic reactions; hormones administered for non-disease-related conditions (e.g., insulin for diabetes); and intermittent use of dexamethasone as an antiemetic or to treat cough associated with everolimus pneumonitis
  • Concurrent antiplatelet agents and prophylactic anticoagulation allowed
  • No prior systemic therapy with a VEGF-binding agent (e.g., bevacizumab)
  • No prior systemic therapy with any mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus)
  • Prior cytokine therapy allowed
  • At least 4 weeks since prior systemic therapy
  • At least 4 weeks since prior major surgical procedure* or open biopsy and fully recovered
  • At least 2 weeks since prior radiotherapy (including palliative) and no concurrent radiotherapy
  • A symptomatic lesion or one which may produce disability (e.g., unstable femur) may be irradiated before study initiation, provided other measurable or evaluable disease is present
  • No concurrent immunosuppressive therapy, including chronic systemic treatment with corticosteroids (≥ 10 mg/day prednisone equivalent)

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

George PhilipsPrincipal Investigator

Trial Sites

U.S.A.
California
  Los Angeles
 Kaiser Permanente Medical Center - Los Angeles
 Han A Koh Ph: 626-564-3455
  San Diego
 Kaiser Permanente - Mission
 Han A Koh Ph: 626-564-3455
  Santa Clara
 Kaiser Permanente Medical Center - Santa Clara Homestead Campus
 Louis Fehrenbacher Ph: 626-564-3455
Florida
  Orange Park
 Integrated Community Oncology Network - Orange Park
 Linda Struhar-Sylvester Ph: 904-861-8574
  Email: info@icononcology.com
Hawaii
  Aiea
 Kapiolani Medical Center at Pali Momi
 Jeffrey L. Berenberg Ph: 808-586-2979
  Honolulu
 Cancer Research Center of Hawaii
 Jeffrey L. Berenberg Ph: 808-586-2979
 Hawaii Medical Center - East
 Jeffrey L. Berenberg Ph: 808-586-2979
 Kapiolani Medical Center for Women and Children
 Jeffrey L. Berenberg Ph: 808-586-2979
 OnCare Hawaii, Incorporated - Kuakini
 Jeffrey L. Berenberg Ph: 808-586-2979
 OnCare Hawaii, Incorporated - Lusitana
 Jeffrey L. Berenberg Ph: 808-586-2979
 Queen's Cancer Institute at Queen's Medical Center
 Jeffrey L. Berenberg Ph: 808-586-2979
 Straub Clinic and Hospital, Incorporated
 Jeffrey L. Berenberg Ph: 808-586-2979
  Kailua
 Castle Medical Center
 Jeffrey L. Berenberg Ph: 808-586-2979
  Lihue
 Kauai Medical Clinic
 Jeffrey L. Berenberg Ph: 808-586-2979
  Wailuku
 Maui Memorial Medical Center
 Jeffrey L. Berenberg Ph: 808-586-2979
 Pacific Cancer Institute - Maui
 Jeffrey L. Berenberg Ph: 808-586-2979
Indiana
  Beech Grove
 St. Francis Hospital and Health Centers - Beech Grove Campus
 Howard M. Gross Ph: 765-983-3000
  Fort Wayne
 Fort Wayne Medical Oncology and Hematology
 Sreenivasa Rao Nattam Ph: 260-484-8830
  Email: ledgar@fwmoh.com
 Radiation Oncology Associates Southwest
 Bharat H. Barai Ph: 219-736-2800
North Carolina
  Concord
 Batte Cancer Center at Northeast Medical Center
 James Grier Wall Ph: 704-355-2884
  Durham
 Duke Cancer Institute
 Jeffrey Crawford Ph: 888-275-3853
North Dakota
  Bismarck
 Bismarck Cancer Center
 John T Reynolds Ph: 701-323-5760
  Email: tfischer@mohs.org
Oregon
  Clackamas
 Clackamas Radiation Oncology Center
 Alison K Conlin Ph: 503-215-6412
  Milwaukie
 Providence Milwaukie Hospital
 Alison K Conlin Ph: 503-215-6412
  Newberg
 Providence Newberg Medical Center
 Alison K Conlin Ph: 503-215-6412
  Oregon City
 Willamette Falls Hospital
 Alison K Conlin Ph: 503-215-6412
  Portland
 CCOP - Columbia River Oncology Program
 Alison K Conlin Ph: 503-215-6412
 Providence Cancer Center at Providence Portland Medical Center
 Alison K Conlin Ph: 503-215-6412
 Providence St. Vincent Medical Center
 Alison K Conlin Ph: 503-215-6412
Pennsylvania
  Abington
 Rosenfeld Cancer Center at Abington Memorial Hospital
 Willard G. Andrews Ph: 215-481-2402
  Bryn Mawr
 Bryn Mawr Hospital
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
  Paoli
 Cancer Center of Paoli Memorial Hospital
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
  Wynnewood
 CCOP - Main Line Health
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
 Lankenau Cancer Center at Lankenau Hospital
 Paul B. Gilman Ph: 484-476-2649
  Email: wellenbachj@mlhs.org
Washington
  Vancouver
 Southwest Washington Medical Center Cancer Center
 Alison K Conlin Ph: 503-215-6412
West Virginia
  Huntington
 Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
 Maria-Rosalia B. Tria Tirona Ph: 304-399-6617
Wisconsin
  Appleton
 Fox Valley Hematology and Oncology - East Grant Street
 Avi Bar-Lev Ph: 920-749-1171

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01198158
ClinicalTrials.gov processed this data on February 11, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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