The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer

A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer

The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).

Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).

• Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
• A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
• A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
• Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
• Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
• The maximum duration of the trial is one year of therapy.

Inclusion Criteria:

• Adenocarcinoma of the prostate with radiographic evidence of metastatic disease.
• Willingness to undergo a baseline tumor biopsy.
• Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT) with evidence of progression on ADT. GnRH therapy will be continued for those on it at baseline
• Patient must have suspected tumor in an area that is safe to biopsy.
• Other prior hormonal interventions or experimental approaches are allowed. These therapies must have been discontinued for a minimum of 28 days with cancer progression.
• Prior or concurrent use of bisphosphonates is allowed.
• One prior non-taxane chemotherapy allowed
• ≥ 3 weeks since major surgery; ≥ 4 weeks since radiotherapy; ≥ 8 weeks since prior strontium-89 or samarium 153
• Performance Status: ECOG 0 or 1
• ANC > 1,500/_l; platelets > 100,000/_l; total Bilirubin < upper limit of normal; AST and ALT < 3 x upper limits of normal; creatinine < 1.5 x upper limits of normal; total fasting cholesterol < 350 mg/dl; total triglycerides < 300 mg/dl

Exclusion Criteria:

• Ongoing oral steroid use. Patients with a history of oral steroid use are eligible as long as the steroids have been discontinued prior to study entry. Ongoing topical and/or inhaled steroid use is allowed.
• Prior taxane chemotherapy
• Prior mTOR inhibitors (RAD001, rapamycin, CCI-779)
• Currently active second malignancy other than non-melanoma skin cancer.
• Ongoing peripheral neuropathy of Grade 2