Impact of Temsirolimus Therapy on Circulating Tumor Cell Biology In Men With Castration Resistant Metastatic Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms; Neoplastic Cells, Circulating
Intervention: Temsirolimus; Diphenhydramine
Intervention description: dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression; Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion
Intervention MeSH terms: Diphenhydramine; Promethazine; Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic; Temsirolimus; prostate; cancer

Summary:

      This is a single arm study of 11 men with treatment refractory metastatic Castrate Resistant
      Prostate Cancer (CRPC) who will receive temsirolimus IV at a dose of 25 mg weekly until
      progression. Progression will not include Prostate Specific Antigen (PSA) progression;
      however, upon PSA progression, the addition of an anti-androgen will be permitted. The
      primary objective of the study is to evaluate change in circulating tumor cell (CTC) counts
      over time in men with metastatic treatment-refractory CRPC in response to temsirolimus
      therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed carcinoma of the prostate. Histologic evidence may be
             confirmed through local or metastatic biopsy review

          -  Radiographic Evidence of metastatic disease

          -  Evidence of disease progression despite castrate levels of testosterone.

          -  A circulating timor cell count using FDA approved CellSearch methodology of ≥ 10 per
             7.5 cc whole blood, drawn within 4 weeks of study registration

          -  Serum PSA greater than or equal to 2ng/dl at registration

          -  At least 4 weeks since prior palliative radiation therapy and/or major surgery, and
             resolution of all toxic effects of prior therapy NCI Common Toxicity Criteria for
             Adverse Effects (CTCAE) Grade less than or equal to 1

          -  Age ≥ 18 years

          -  Adequate laboratory parameters

          -  Karnofsky Performance Status ≥ 60

          -  Life expectancy of at least 3 months

        Exclusion Criteria:

          -  History of or active central nervous system metastases

          -  The use of cytotoxic, biologic, or hormonal therapies within 4 weeks of study entry.

          -  Subjects receiving known strong Cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors
             and/or inducers

          -  Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the
             screening visit

          -  Have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation
             therapy.

          -  Presence of non-healing wound or ucer

          -  Grade ≥ 3 hemorrhage in the past month to study entry

          -  Hypertension with systolic blood pressure of ≥ 180 mmHg and/or diastolic pressure ≥
             100 mmHg (Anti-hypertensive medications are permitted)

          -  Subjects with Class 2-4 heart disease or any history of congestive heart failure with
             an ejection fraction <50% or a recent (within 12 months) cardiovascular event.

          -  Anticoagulation with warfarin

          -  Diabetes mellitus with glycosylated hemoglobin A1c ≥ 10% despite therapy

          -  History of interstitial pneumonitis

          -  Subjects with active autoimmune disorder(s) being treated with immunosuppressive
             agents within 4 weeks prior to screening visit

          -  Subjects receiving immunosuppressive agents and those with chronic
             viral/bacterial/fungal illnesses. Replacement doses of corticosteroids are permitted.

          -  Active infection(s), active antimicrobial therapy or serious intercurrent illness.

          -  History of other prior malignancy in past 5 years, other than basal cell carcinoma,
             squamous cell carcinoma of the skin, cervical carcinoma in sity, localized prostate
             cancer, or superficial bladder cancer.

          -  Agreement to use medically acceptable contraceptive methods while on study and for 3
             months after the last dose of temsirolimus.

          -  Any other major medical or psychiatric illness that, in the investigator's judgment,
             will substantially increase the risk associated with the subject's participation in
             this study, including inability to absorb oral medications.

          -  Known hypersensitivity to any of the components in the temsirolimus infusion or other
             medical reasons for not being able to receive adequate premedication.

          -  Corrected QT interval on baseline EKG of >500 milliseconds

          -  the use of agents that significantly prolong the Corrected QT interval and who are
             unable to stop medications prior to study initiation.

          -  Prior exposure to an Mammalian Target of Rapamycin (mTOR) inhibitor

          -  Presence of nephrotic syndrome as determined by clinical evaluation of 24 hour urine.