Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel

This is an interventional treatment trial for Prostate Cancer focused on measuring hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer, adenocarcinoma of the prostate Read More

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