Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: carboplatin; RAD 001; prednisone; laboratory biomarker analysis; pharmacological study
Intervention description: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle; 5 mg orally starting on Day 2 then continuous; 5 mg orally twice a day starting on Day 1 then continuous; Samples will be collected from archival tissue.; Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2
Intervention MeSH terms: Prednisone; Carboplatin; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: Male
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: hormone-resistant prostate cancer; recurrent prostate cancer; stage IV prostate cancer; adenocarcinoma of the prostate

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin and prednisone, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Giving carboplatin together
      with everolimus and prednisone may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving carboplatin together with everolimus
      and prednisone works in treating patients with metastatic prostate cancer that progressed
      after docetaxel.
    

Eligibility 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