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Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RAD001 (Everolimus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00651482
Recruitment Status : Terminated (slow accrual)
First Posted : April 2, 2008
Results First Posted : July 29, 2014
Last Update Posted : April 11, 2017
Genentech, Inc.
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University

Brief Summary:
To determine the safety and efficacy of the combination of bevacizumab and everolimus (RAD001) for the treatment of metastatic renal cell cancer

Condition or disease Intervention/treatment Phase
Kidney Neoplasms Kidney (Renal Cell) Cancer Drug: Everolimus Drug: Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RAD001 (Everolimus)
Study Start Date : August 2008
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: Bevacizumab + RAD001 (everolimus)

Study treatment, consisting of bevacizumab + everolimus, was administered as 28-day cycles

Bevacizumab 10 mg/kg administered by IV infusion every 14 days (dose suspension permitted, dose reduction not permitted)

Everolimus 10 mg daily was administered orally (dose reduction to 5 mg daily and then 5 mg every other day, was permitted as needed for toxicity or tolerability)

Drug: Everolimus
Other Names:
  • Zortress
  • Certican
  • RAD001

Drug: Bevacizumab
Other Name: Avastin

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: 24 months ]
    Progression-free survival (PFS) per RECIST criteria

Secondary Outcome Measures :
  1. Objective Response (OR) [ Time Frame: 24 months ]
    Number of subjects with objective response (OR)

  2. Objective Response (OR) Duration [ Time Frame: 24 months ]
  3. Time-to-Treatment Failure (TTF) [ Time Frame: 24 months ]
  4. Overall Survival (OS) [ Time Frame: 44 months ]
  5. Number of Subjects With Drug-related SAEs [ Time Frame: 24 months ]
  6. Total Number of Drug-related SAEs [ Time Frame: 24 months ]
  7. Treatment Discontinuation Due to Toxicity [ Time Frame: 24 months ]
    Number of subjects whose treatment was discontinued due to toxicity

  8. Treatment Discontinuation Due to Disease Progression [ Time Frame: 24 months ]
    Number of subjects whose treatment was discontinued due to disease progression

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed Informed Consent Form
  • Histologically confirmed metastatic RCC that is predominantly clear cell Measurable disease, as defined by RECIST
  • Age ≥ 18 years
  • ECOG performance status of 0 or 1
  • No more than 1 prior targeted therapy (eg, sorafenib, sunitinib) (prior cytokine therapy allowed)
  • No more than 2 prior systemic therapies
  • Ability and capacity to comply with the study and follow-up procedures

General Exclusion Criteria

  • Inability to comply with study and/or follow-up procedures
  • Life expectancy of < 12 weeks
  • Inadequate organ function, as evidenced by any of the following at screening:

    • Absolute neutrophil count (ANC) < 1500/uL
    • Platelet count ≤ 100 x 10^9/L
    • Total bilirubin ≥ 1.5 x upper limit of normal (ULN)
    • AST and/or ALT > 2.5 x ULN for patients without evidence of liver metastases, or 5 x ULN for patients with documented liver metastases
    • Serum creatinine > 2.0 mg/dL
    • Hemoglobin < 9 g/dL (may be transfused or receive epoetin alfa to maintain or exceed this level)
  • Active infection or fever > 38.5°C within 3 days of starting treatment
  • Women who are pregnant or breast feeding,
  • Able to conceive and unwilling to practice an effective method of birth control.
  • History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, early-stage bladder cancer, or low-grade endometrial cancer
  • Malignancies that have undergone a putative surgical cure (i.e., localized prostate cancer post-prostatectomy) within 5 years prior to Day 1 may be discussed with the Principal Investigator.
  • Any other medical conditions (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

Disease-Specific Exclusion Criteria

  • RCC with predominantly sarcomatoid features
  • Radiotherapy for RCC within 28 days prior to Day 1, with the exception of single-fraction radiotherapy given for the indication of pain control
  • Prior treatment with bevacizumab or any mTOR inhibitor (eg, temsirolimus, sirolimus, or everolimus)
  • Current need for dialysis

Bevacizumab-Specific Exclusions

  • Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Known CNS disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; 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 3 months prior to Day 1 will be excluded.
  • Significant vascular disease (eg, aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy that is not intentionally pharmacologically-induced
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by a urine protein:
  • Creatinine (UPC) ratio ≥ 1.0. If UPC ratio ≥ 1.0, the patient must undergo a 24 hour urine collection which must demonstrate ≤ 1g of protein in 24 hours to be eligible.
  • Known hypersensitivity to any component of bevacizumab

RAD001-Specific Exclusion Criteria

  • Known hypersensitivity to any component of RAD001
  • Chronic treatment with systemic steroids or another immunosuppressive agent
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Severely impaired lung function (spirometry and DLCO < 50% of normal and O2 saturation 88% or less at rest on room air)
  • If O2 saturation is ≤ 88% at rest on screening, pulmonary function tests (PFTs) will be ordered to confirm normal pulmonary function and eligibility.
  • Fasting total cholesterol > 350 mg/dL
  • Fasting triglyceride level > 400 mg/dL or >2.5 x ULN
  • Fasting serum glucose > 250 mg/dL
  • Serum phosphorus < 2.0 mg/dL
  • Serum corrected calcium < 8.0 mg/dL

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00651482

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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Sandy Srinivas
Genentech, Inc.
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Principal Investigator: Dr. Sandy Srinivas Stanford University
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Responsible Party: Sandy Srinivas, Associate Professor, Stanford University Identifier: NCT00651482    
Other Study ID Numbers: IRB-11789
RENAL0016 ( Other Identifier: OnCore )
98593 ( Other Identifier: Stanford University Alternate IRB Approval Number )
AVF4304s ( Other Identifier: Genentech-Roche )
41839 ( Other Identifier: Novartis, Inc )
First Posted: April 2, 2008    Key Record Dates
Results First Posted: July 29, 2014
Last Update Posted: April 11, 2017
Last Verified: March 2017
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors