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Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
This study is currently recruiting participants.
Verified February 2012 by National Cancer Institute (NCI)

First Received on September 8, 2010.   Last Updated on February 9, 2012   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01198158
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Kidney Cancer
Biological: bevacizumab
Drug: everolimus
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial Comparing Everolimus Plus Placebo Versus Everolimus Plus Bevacizumab for Advanced Renal Cell Carcinoma Progressing After Treatment With Tyrosine Kinase Inhibitors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Objective response rate (defined as confirmed complete response plus partial response) [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 700
Study Start Date: September 2010
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive oral everolimus once daily on days 1-28 and placebo IV over 30-90 minutes on days 1 and 15.
Drug: everolimus
Given orally
Other: placebo
Given IV
Experimental: Arm II
Patients receive oral everolimus once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15.
Biological: bevacizumab
Given IV
Drug: everolimus
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • To compare the overall survival of patients receiving everolimus with vs without bevacizumab among patients with advanced renal cell carcinoma that progressed after first-line VEGFR-tyrosine kinase inhibitor treatment.

Secondary

  • To compare the progression-free survival and proportion of patients who experience an objective response (defined as confirmed complete response plus partial response) in patients receiving everolimus with vs without bevacizumab.
  • To compare grade 3 or higher toxicity in patients receiving everolimus with vs without bevacizumab.

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 oral everolimus once daily on days 1-28 and placebo IV over 30-90 minutes on days 1 and 15.
  • Arm II: Patients receive oral everolimus once daily on days 1-28 and bevacizumab 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 thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • See Patient Characteristics
  • 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)
  • 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 NOTE: *The following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, and routine dental procedures.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01198158

  Show 381 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Principal Investigator: George Philips, MD, MPH University of Vermont
  More Information

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT01198158     History of Changes
Other Study ID Numbers: CDR0000684313, CALGB-90802
Study First Received: September 8, 2010
Last Updated: February 9, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent renal cell cancer
stage IV renal cell cancer
stage III renal cell cancer
clear cell renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on May 23, 2012