Neoadjuvant Everolimus (RAD001) For Advanced RCC before Cytoreductive Nephrectomy, With Correlative Tumor Studies

Summary

This is a multicenter, pilot, open-label phase II trial of neoadjuvant everolimus for 3-5 weeks followed by cytoreductive nephrectomy for metastatic renal cell carcinoma followed by everolimus treatment until disease progression per the response evaluation criteria in solid tumors (RECIST). This is a non-randomized single stage Phase II trial. All subjects will receive the same procedures and treatment. Subjects will take one 10 mg tablet of Everolimus by mouth at the same time every day for 3 to 5 weeks. The study will be open to enrollment approximately 24 months. (NOTE: we are using the 3-5 week time frame to allow time for scheduling the cytoreductive nephrectomy).

The primary endpoint of this trial is progression free survival (PFS), which will be summarized descriptively by the number and percentage of patients who are progression free at the end of 4 months (16 weeks).

The accrual goal is 27-patients with Baylor College of Medicine and University of Texas Southwestern Medical School enrolling approximately 14 each. All patients must be deemed surgical candidates by a urologist and if deemed necessary by the urologist, clearance by an internist must be provided before patients are enrolled. Patients must have baseline evaluations performed prior to enrollment and must meet all inclusion and exclusion criteria. Once it has been determined that the patient meets the study specifications (except for histological confirmation of RCC), the patient will be asked to give informed consent, and biopsies may be performed. Biopsies have to be performed no later than 4 weeks from the first set of imaging studies. If biopsies fail to show RCC of pre-specified histologies, the patient will be considered not evaluable. Results of all baseline evaluations, including scans (CT of the chest, abdomen and pelvis as well as brain MRI) and blood work, which assure that all inclusion and exclusion criteria have been satisfied, must be reviewed by the Principal Investigator or his/her designee prior to enrollment of a patient.

Participant Eligibility

 Proven metastatic) RCC
 Histology: clear cell, papillary or chromophobe
 3 out 6 risk factors (by MSKCC criteria and one additional criterion: multiple sites of metastasis) or not candidates for or refuse sunitinib.
 Patients must be deemed surgical candidates for cytoreductive nephrectomy( open or laparoscopic) by the urologist. If the urologist deems a medicine evaluation necessary prior to establishing that the patient is a candidate for surgery, the evaluation must be performed prior to enrollment and only if the patient is cleared will the patient be eligible to enter into the trial.
 Age ≥ 18 years
 EGOG PS 0-2
 Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >8 g/dL
 Adequate liver function as shown by:
- serum bilirubin ≤ 1.5 x ULN
- INR < 1.3 (or < 3 on anticoagulants)
- ALT and AST ≤ 3x ULN
 Adequate renal function: serum creatinine ≤ 1.5 x ULN
 Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 400 mg/dL. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication (note: drugs metabolized through the CYP3A4 should be avoided; see Table 3-3)
 Signed informed consent
- Radiation therapy must have occurred at least one week prior to initiation of treatment with Everolimus
- Primary tumor is considered amenable to surgical extirpation by the attending surgeon
- Thrombosis of the inferior vena cava below the hepatic veins are allowed