Phase II Trial of Carboplatin and RAD001 in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy.

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic adenocarcinoma of the prostate

- Objective disease progression or rising PSA despite androgen deprivation therapy and
antiandrogen withdrawal (when applicable)

- Progressed after ≥ 1 prior docetaxel-based chemotherapy regimen for metastatic
disease

- Patients with measurable disease* must have either rising PSA, increase in size
of the lesion(s), or both

- Patients with rising PSA as the only evidence of disease progression must
demonstrate a rising trend with 2 successive elevations ≥ 1 week apart

- Patients with no measurable disease must have a PSA ≥ 5 ng/mL or new areas of
bony metastases on bone scan NOTE: *There is no minimum PSA requirement for
patients with measurable disease

- Documented to be castrate with a testosterone level of ≤ 0.5 ng/mL

- Leuteinizing hormone-releasing hormone agonist therapy must be continued, if
required to maintain castrate levels of testosterone

- No uncontrolled brain or leptomeningeal metastases, including patients who continue
to require glucocorticoids for brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- ANC ≥ 1,500/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Platelet count ≥ 100,000/mm^3

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Calculated creatinine clearance ≥ 50 mL/min OR serum creatinine ≤ 2 mg/dL

- AST and/or ALT ≤ 2.5 times ULN if alkaline phosphatase normal OR alkaline phosphatase
≤ 4 times ULN if AST and/or ALT normal (for patients without documented bone
metastases or for patients with liver metastases)

- AST and/or ALT < 2.5 times ULN, without regard to alkaline phosphatase levels (for
patients with documented bone metastases)

- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤
2.5 times ULN (in the case that one or both of these thresholds are exceeded, the
patient is eligible only after initiation of appropriate lipid-lowering medication)

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- Willing and able to comply with this study

- Able to ingest oral medication

- No other malignancies except non-melanoma skin cancer or any other adequately treated
cancer in complete remission for ≥ 2 years

- No significant traumatic injury within the past 4 weeks

- No active (acute or chronic) or uncontrolled severe infections

- No severe and/or uncontrolled medical conditions or other conditions that could
affect study participation, including the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within the past 6 months, serious uncontrolled cardiac arrhythmia, or
any other clinically significant cardiac disease

- Severely impaired lung function as defined by spirometry and DLCO that is 50% of
the normal predicted value and/or oxygen saturation that is ≤ 88% at rest on
room air

- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN

- Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis

- Known history of HIV seropositivity, hepatitis B or C

- Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of everolimus (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection)

- Active, bleeding diathesis

- No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus)
or to their excipients

- No history of noncompliance to medical regimens

- No uncontrolled diabetes mellitus

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 1 prior docetaxel based regimen for metastatic disease

- Docetaxel based combination therapy or docetaxel alone considered as 1 regimen

- No more than 2 prior chemotherapy regimens for metastatic disease

- No prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)

- At least 6 weeks since prior bicalutamide or nilutamide

- At least 4 weeks since prior flutamide

- More than 4 weeks since prior and no other concurrent investigational drugs

- More than 4 weeks since prior and no other concurrent anticancer therapies (including
chemotherapy, radiotherapy, or antibody-based therapy)

- More than 4 weeks since prior and no concurrent major surgery (defined as requiring
general anesthesia) and recovered

- More than 1 week since prior and no concurrent immunization with attenuated live
vaccines

- No concurrent chronic, systemic treatment with corticosteroids or other
immunosuppressive agents

- Topical or inhaled corticosteroids are allowed

- No concurrent prophylactic growth factors

- Concurrent bisphosphonate therapy allowed