Carcinoma, Renal Cell
Conditions
Keywords
Renal cell carcinoma, Metastatic, everolimus, neo-adjuvant, biomarkers, nephrectomy, Locally advanced clear cell renal carcinoma, Metastatic clear cell renal carcinoma, Clear Cell Renal Carcinoma
Brief summary
This study will gather data on potential biomarkers in the treatment of advanced renal cell carcinoma (kidney cancer) and investigate their use as indicators of disease response. The results could eventually enable doctors to match levels of therapy to levels of biomarker on an individual basis and to increase the chance of disease response in patients. This study will also test a new paradigm in the treatment approach of advanced kidney cancer by using the drug everolimus in a neo-adjuvant setting, with the overarching goal of decreasing cancer recurrence rates and improving patient outcomes and survival.
Interventions
DRUGeverolimus
10 mg/ day everolimus in the form of an oral tablet for 12 weeks leading up to nephrectomy (with a 1-week perioperative washout period) in patients with locally advanced disease and re-initiating the drug postoperatively in patients with metastatic disease for up to 24 months, or until disease progression. Dosage may be reduced at any point to 5 mg/ day in the event of any grade 3/ 4 toxicity.
Sponsors
McMaster University
Novartis Pharmaceuticals
St. Joseph's Healthcare Hamilton
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age and capable of giving informed consent * Radiological evidence of RCC consisting of: CT scan with stage T2, T3, T3a, T3b, T4, or any stage T with N1/ 2 and/ or metastatic disease * Having a nephrectomy and willing to have a kidney biopsy * ECOG score 0 or 1 * Clear cell histology * Negative for HIV, Hepatitis B, and Hepatitis C * Negative pregnancy test for women of child-bearing potential
Exclusion criteria
* Stage T1 disease without metastases * Abnormal laboratory values at screening within the following ranges: * Absolute neutrophil count ≤ 1.5 × 109/ L; Platelet count ≤ 100 × 109/ L * Leukocyte count ≤ 3 × 109/ L; Hemoglobin ≤ 80 g/ L; Serum creatinine ≥ 2.0 × the upper normal limit (UNL); Total bilirubin ≤ 1.5 × UNL; AST and ALT ≤ 3.0 × UNL * Fasting serum cholesterol ≤ 9.0 mmol/ L; Fasting serum triglycerides ≥ 5.0 mmol/L * Any major illness that, based on the investigator's judgment, will substantially increase the risk associated with a subject's participation in this study * Other currently active malignancies * Currently taking any medications known to interfere with the metabolism of everolimus * Receiving anticoagulation with warfarin * A history of pulmonary hypertension or interstitial lung disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response of primary tumor and metastases (if applicable) to everolimus in terms of tumor size and appearance (RECIST imaging response criteria) as determined by CT or MRI | From 6 weeks after starting neo-adjuvant everolimus until 1 year post-nephrectomy (or up to 24 months post-nephrectomy in metastatic patients) |
Secondary
| Measure | Time frame |
|---|---|
| Effect of everolimus on blood and tissue biomarker expression (periodic blood testing and tissue samples from baseline renal biopsy and nephrectomy) in and among patients with locally advanced and metastatic disease with respect to baseline values | From baseline to 1 year post-nephrectomy for blood biomarker levels and from baseline to nephrectomy (week 12) for tissue biomarker levels |
Countries
Canada
Outcome results
None listed