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A Comparison of Blood and Tissue Biomarkers Before and After Nephrectomy in the First-line Setting With Everolimus in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

Phase 2
18 Years
Open (Enrolling)
Clear-cell Renal Carcinoma, Clear-cell Metastatic Renal Cell Carcinoma

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Trial Information

A Comparison of Blood and Tissue Biomarkers Before and After Nephrectomy in the First-line Setting With Everolimus in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

An open-label, exploratory, single-arm, multicenter trial. Treatment with everolimus will be
initiated once patients have undergone baseline screening and provided their written
informed consent.

Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest
period prior to surgery. The starting dose will be 10 mg daily with provision for dose
reduction based on tolerability.

Radical nephrectomy will be performed at the end of week 7. For metastatic patients, two to
four weeks after surgery, everolimus will be reintroduced. Treatment will be continued until
disease progression, unacceptable toxicity, withdrawal of patient consent, or other stopping
rules are met.

Patients with locally advanced renal carcinoma will stop drug intake before nephrectomy.

Resumption of everolimus may be postponed in cases of a delay in wound healing or surgical

After treatment discontinuation and the last treatment visit (28-days after the last dose),
patients will be followed up in order to collect data on the onset of progression and
survival. In metastatic patients discontinuing treatment for reasons other than disease
progression, tumor assessment will continue every 3 months, until disease progression or
initiation of other anticancer therapy for up to one year of follow-up.

Inclusion Criteria:

- Advanced RCC or a resectable renal tumor and at least one measurable inoperable
metastasis (at least 1 cm), in whom anti-angiogenic therapy is indicated

- Patients without target lesions, with bone metastasis

- Histologically confirmed clear cells RCC and possibility of adequate tumor sampling
prior to treatment

- No prior systemic treatment for RCC

- Male or female, at least 18 years

- PS ECOG 0-1

- Life expectancy at least 3 months

- Adequate organ function with the following criteria:

- Total serum bilirubin equal or less than 2 x ULN (Gilbert's disease exempted)

- Serum transaminases and alkaline phosphatases equal or less than 2.5 x ULN, or
in case of liver or bone metastasis equal or less than 5x ULN

- Serum creatinine equal or less than 2 x ULN, creatinine clearance at least 50

- Absolute neutrophil count (ANC) at least 1500/mm3

- Platelets at least 100,000/mm3

- Hemoglobin at least 10.0 g/dL

- INR equal or less than 1.7 or prothrombin time (PT) equal or less than 6 sec

- Blood glucose less than 1.5x ULN

- Fasting cholesterol equal or less than 5 mmol/L, triglycerides equal or less
than 200 mg/dl,

- Negative pregnancy test within 7 days prior to enrollment

- Signed and dated IRB/ICE-approved informed consent form

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.

- Patient covered by the national health system

Exclusion Criteria:

- Previous nephrectomy

- Histology: any histologic type different than ccRCC

- Treatment in a clinical trial in the last 30 days

- Previous treatment with everolimus or other mTOR-inhibitors and anti-angiogenic drugs

- Any of the following within 12 months prior to treatment initiation: severe/unstable
angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive
heart failure, ischemic or hemorrhagic stroke including transient ischemic attack,
abnormal lung function.

- Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic
pressure >90 mmHg, despite optimal medical treatment

- Abnormal ECG (Clinically significant)

- Treatment with vitamin K antagonists. Ongoing treatment with therapeutic doses of
coumarin derivative anticoagulants (e.g. warfarin) or treatment within the 2 weeks
before the first day of everolimus administration. Prophylaxis with low dose warfarin
for deep vein thrombosis is permitted (up to 2 mg/day). Low molecular weight heparin
is allowed.

- Brain metastasis. (Brain scan or MRI is mandatory). Note: Previous treated brain
metastasis (surgery ± radiotherapy, radiotherapy, radiosurgery or gammaknife) and
satisfying the following three criteria are allowed:

- Asymptomatic;

- No evidence of any active brain metastasis 3 months prior inclusion;

- No necessity of corticoid or antiepileptic treatment.

- Pregnancy or breastfeeding.

- Any second malignancy within the last 3 years with the exception of basal cell
carcinoma, in situ cervical cancer and pT1/a bladder cancer with no evidence of
recurrent disease for 12 months.

- Clinically significant gastrointestinal abnormalities including but not limited to:

- Malabsorption syndrome

- Major resection of the stomach or small bowel that could affect the absorption
of the study drug

- Active peptic ulcer disease

- Inflammatory bowel disease

- Ulcerative colitis or other gastrointestinal conditions with increased risk of

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 28 days prior to beginning study treatment

- Hepatitis B/C

- Hypersensitivity to everolimus or any excipient of everolimus.

- Any active (acute or chronic) or uncontrolled infection/disorders that impair the
ability to evaluate the patient or for the patient to complete the study.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

Objective clinical benefit

Outcome Description:

Objective clinical benefit is defined as complete response, partial response or stable disease according to RECIST criteria version 1.1

Outcome Time Frame:

After 6 weeks of treatment

Safety Issue:


Principal Investigator

Stéphane Oudard, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hôpital Européen Georges Pompidou, Paris (France)


France: Agence Nationale de Sécurité du Médicament et des produits de santé

Study ID:




Start Date:

June 2012

Completion Date:

Related Keywords:

  • Clear-cell Renal Carcinoma
  • Clear-cell Metastatic Renal Cell Carcinoma
  • Clear cells renal carcinoma
  • everolimus
  • neo-adjuvant treatment
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms