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Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RADOO1

Phase 2
18 Years
Not Enrolling
Kidney Neoplasms, Kidney (Renal Cell) Cancer

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Trial Information

Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RADOO1

Inclusion Criteria:

Patients will be included in the study based on the following criteria:

- Signed Informed Consent Form

- Histologically confirmed metastatic RCC that is predominantly clear cell

- Measurable disease, as defined by RECIST (see Appendix D)

- Age >= 18 years

- ECOG performance status of 0 or 1

- No more than one prior targeted therapy (e.g. sorafenib, sunitinib)

o Prior cytokine therapy allowed

- No more than two prior systemic therapies

- Ability and capacity to comply with the study and follow-up procedures

Exclusion Criteria:

1. Disease-Specific Exclusions

- 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 (temsirolimus, sirolimus,
or everolimus)

- Current need for dialysis

2. General Medical Exclusions

Subjects meeting any of the following criteria are ineligible for study entry:

- Inability to comply with study and/or follow-up procedures

- Life expectancy of less than 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 ULN

- Alkaline phosphatase, AST, and/or ALT > 2.5 x the upper limit of normal (ULN)
for patients without evidence of liver metastases; > 5 X ULN for patients with
documented liver metastases

- Serum creatinine > 2.0 mg/dL

- Hemoglobin < 9 g/dL a. may be transfused or receive epoetin alfa to maintain or
exceed this level up to the hemoglobin level recommended on the current label
for for epoetin alfa because of the potential increased risk of thrombotic
events and increased mortality. Also, rapid increase in hemoglobin may
exacerbate hypertension, i.e., a possible adverse event with bevacizumab and to
a lesser extent with RAD001.

- Active infection or fever > 38.5°C within 3 days of starting treatment

- Women who are pregnant or breast feeding, or women/men able to conceive and unwilling
to practice an effective method of birth control.

- Women of childbearing potential must have a negative urine or serum pregnancy
test within 7 days prior to the initial administration of RAD001 and the first
day of each cycle.

- Oral, implantable, or injectable contraceptives may be affected by cytochrome
P450 interactions, and are therefore not considered effective methods of birth
control for this study.

- 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 c. 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 (see
Appendix B)

- History of myocardial infarction or unstable angina within 6 months prior to study

- History of stroke or transient ischemic attack within 6 months prior to study

- Known CNS disease, except for treated brain metastasis

o 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 (e.g., aortic aneurysm, aortic dissection)

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy that is not intentionally

- 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 >= 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

d. RAD001- Specific Exclusions

- 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 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

- Severely impaired lung function (spirometry and DLCO 50% or less 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 >2.5x ULN

- Fasting serum glucose > 250 mg/dl

- Serum phosphorus < 2.0 mg/dl Serum corrected calcium < 8.0 mg/dL

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To assess the effect of the combination therapy bevacizumab and RAD001 on progression-free survival in treatment-refractory mRCC using Response Evaluation Criteria in Solid Tumors (RECIST

Outcome Time Frame:


Safety Issue:


Principal Investigator

Dr. Sandy Srinivas

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Food and Drug Administration

Study ID:




Start Date:

August 2008

Completion Date:

March 2012

Related Keywords:

  • Kidney Neoplasms
  • Kidney (Renal Cell) Cancer
  • Neoplasms
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms



Stanford University School of Medicine Stanford, California  94305-5317